Abstract Antibody-drug conjugates (ADC), precisely deliver a cytotoxic agent to antigen-expressing tumor cells by using specific binding strategies of antibodies. The ADC has shown the ability of potent bio-therapeutics development but indefinite stoichiometric linkage and full-length antibody penetration compromised the field of its advancement. Single chain variable fragments convention instead of the full-length antibody may overcome the challenge of rapid penetration and internalization. Programmed cell death ligand-1 interaction with PD-1 has recently revolutionized the field of immunotherapy. We systematically designed scPDL1-DM1 drug conjugate by linking scFv-PD-L1 proteins (scFv) with maytansinoids (DM1) cytotoxic agent through succinimidyl trans-4-maleimidylmethyl cyclohexane-1- carboxylate (SMCC) linker. Binding affinity was confirmed by immunocytochemistry, spectrophotometry and gel electrophoresis analysis. The scPDL1-DM1 showed specific binding with PD-L1 positive tumor cells and retained in vitro anti-cell proliferation activity. The intracellular trafficking of the drug was evaluated in A549 cancer cell lines, and maximum trafficking was observed after two hours of incubation. The generated drug can be utilized as a potent tool for site-specific conjugation, predicting specificity in vitro activities with extended range against PD-L1 positive cancer cells and can be utilized for further in vivo testing and clinical therapeutics development.

Three crime data sources were collected and merged for this study. All three crime sources were either only reporting on the U.S. state of Kentucky (KOOL and Louisville Open Data), or filtered to only contain results for the U.S. state of Kentucky (FBI). Each data source contains unique features such as crime classifications, and unique challenges in collection and cleaning.

The United States Federal Bureau of Investigation (FBI) issues a variety of query-able crime related data on their website. This data is sourced from law enforcement agencies across the U.S. as part of their National Incident-Based Reporting System (NIBRS) and its standards. The goal of gathering, standardizing, and providing this information is to facilitate research into crime and law enforcement patterns. The information is provided as a collection of CSV files with instructions and code for importing into a SQL database. For the purposes of this research, we utilized the the crime databases for the years 2017, 2018 and 2019, containing a total of 1,939,990 unique incidents. The NIBRS_code property denotes the type of crime as assigned by the reporting agency. The human trafficking codes are 40A (Prostitution), 40B (Assisting or Promoting Prostitution), and 370 (Pornography/Obscene Material). The drug incidents were found using codes 35A (Drug/Narcotic Violations) and 35B (Drug Equipment Violations).

The Kentucky Department of Corrections, as a service to the public, provides an online lookup of people currently in its custody called Kentucky Offender Online Lookup (KOOL). This web application offers users tools to search for sets of inmates based on features such as name, crime date, crime name, race, and gender. The data that KOOL searches contains only people who are currently under supervision of the state of Kentucky (or should be under supervision in the case of escape).

The Louisville Open Data Initiative (LOD) is a program from the city of Louisville, Kentucky, U.S.A. to increase the transparency of the city government and promote technological innovation. As part of LOD, a dataset of crime reports is made available online. The records contained within the LOD dataset represent any call for police service where a police incident report was generated. This does not necessarily mean a crime was committed, as an incident report can be generated before an investigation has taken place.

Die Auswirkungen von Drogen auf Gemeinschaften. Themen: Bewertung des Drogenkonsums oder -handels im persönlichen Umfeld als ernstes Problem; Probleme im Zusammenhang mit Menschen, die in ihrem persönlichen Umfeld Drogen konsumieren oder damit handeln: zu leichte Verfügbarkeit von Drogen, harte Drogen konsumierende Menschen, an öffentlichen Plätzen Cannabis rauchende Menschen, Drogen konsumierende Kinder oder Teenager, Drogendealer oder -konsumenten mit einschüchterndem Verhalten, Konflikte und Gewalt im Zusammenhang mit Drogenkonsum, häusliche Gewalt im Zusammenhang mit Drogenkonsum, Verkehrsunfälle im Zusammenhang mit Drogenkonsum, Armut und Arbeitslosigkeit im Zusammenhang mit Drogenkonsum; Bedeutung des Drogenkonsums in Bezug auf jede der folgenden Arten von Kriminalität in der persönlichen Umgebung: Jugendkriminalität, Stehlen und (Einbruch-)Diebstahl, Gewaltverbrechen und Mord, Korruption und mangelndes Vertrauen in öffentliche Beamte und Institutionen; Entwicklung der Drogenproblematik im persönlichen Umfeld in den letzten Jahren; Auswirkungen der COVID-19-Pandemie auf den Konsum illegaler Drogen im persönlichen Umfeld und auf Drogenprobleme im persönlichen Umfeld; Einstellung zu den folgenden Aussagen über die Verfügbarkeit und den Konsum von Drogen: Befragte/r fühlt sich in der Nähe von Wohnung, Schule oder Arbeitsplatz unsicher, haben negative Auswirkungen auf die persönlichen Beziehungen, haben negative Auswirkungen auf persönliche Gesundheit und Wohlbefinden, sind von zentraler Bedeutung für die Verringerung der allgemeinen Lebensqualität im persönlichen Umfeld; Bewertung der Auswirkungen des Online-Drogenverkaufs auf die Probleme im persönlichen Umfeld; Bewertung der Schwere der durch Cannabis verursachten Gesundheitsprobleme; Einstellung zur Zulassung von Zulassung von Cannabis für: weder medizinische Zwecke noch für den Freizeitgebrauch, medizinische Verwendung nur auf ärztliche Verschreibung, medizinische Verwendung ohne ärztliche Verschreibung, sowohl medizinischen als auch Freizeitgebrauch für Erwachsene; bereits getätigter Cannabiskonsum; Schwierigkeit, die folgenden Substanzen innerhalb von 24 Stunden zu beschaffen: Cannabis, Kokain, MDMA (Ecstasy), Heroin, legale Rauschmittel; Einstellung zum Verbot oder zur gesetzlichen Regulierung der vorgenannten Substanzen. Demographie: Alter; Geschlecht; Staatsangehörigkeit; Urbanisierungsgrad; Alter bei Beendigung der Ausbildung; Beruf; berufliche Stellung; Besitz eines Mobiltelefons; Festnetztelefon im Haushalt; Haushaltszusammensetzung und Haushaltsgröße. Zusätzlich verkodet wurde: Befragten-ID; Land; Interviewmodus (Mobiltelefon oder Festnetz); Region; Nationengruppe; Gewichtungsfaktor. The impact of drugs on communities. Topics: assessment of people using or dealing drugs in the personal local area as a serious problem; problems associated with people using or dealing drugs in the personal local area: drugs being too easily available, people taking hard drugs, people smoking cannabis in public places, children and teenagers taking drugs, drug dealers or users being intimidating to local people, conflict and violence in the community related to drug use, domestic violence related to drug use, traffic accidents related to drug use, poverty and unemployment related to drug use; importance of drug use with regard to each of the following types of crime in the personal local area: youth crime, stealing / theft and burglary, violent crime and murder, corruption and lack of trust in public officials and institutions; development of the problems caused by drugs in the personal local area in the last few years; impact of the COVID-19 pandemic on the use of illegal drugs in the personal local area and on drug problems in the personal local area; attitude towards the following statements regarding the availability and the use of drugs: make respondent feel unsafe near his / her home or school or place of work, have a negative impact on personal relationships, have a negative impact on personal health and well-being, are central to reducing the overall quality of life in the personal local area; assessment of the impact of online drug sales on the problems in the personal local area; assessment of the severeness of health problems caused by cannabis; attitude towards the allowance of cannabis for: neither medical nor recreational use, medical use only under medical prescription, medical use only without prescription, both medical and recreational use for adults; personal use of cannabis; difficulty to obtain the following substances within 24 hours: cannabis, cocaine, MDMA (ecstasy), heroin, legal highs; attitude towards banning the sale of the aforementioned substances. Demography: age; sex; nationality; type of community; age at end of education; occupation; professional position; own a mobile phone and fixed (landline) phone; household composition and household size. Additionally coded was: respondent ID; country; type of phone line; region; nation group; weighting factor.

FDA Orange Book Drug Data

Pharmaceutical drug information with patent and exclusivity details

By Basil Hayek [source]

About this dataset

The dataset consists of three main files: patents.csv, reference.csv, and products.csv. The patents.csv file provides information on patent details such as patent numbers, expiration dates, and patent use codes for pharmaceutical drugs listed in the FDA Orange Book. The reference.csv file serves as a reference guide for the exclusivity codes used in the dataset, providing their corresponding meanings and explanations. Lastly, the products.csv file contains comprehensive information about various pharmaceutical drugs including their ingredients, trade names, applicants (companies or organizations), strengths or concentrations, approval dates from the FDA.

Key columns found within these datasets include:

• Applicant_Full_Name: The full name of the company or organization that submitted the application for a particular drug.
• Product_No: A unique numeric identifier assigned by the FDA to each drug product.
• Patent_Expire_Date_Text: The expiration date of the patent associated with a specific drug.
• Delist_Flag: Indicates whether a particular drug has been delisted by the FDA.
• DF;Route: Represents both dosage form and route of administration for a given drug.
• Strength: Indicates concentration or strength of active ingredients present in a particular drug product.
• RS (Reference Standard): A benchmark against which quality measurements are made for each drug's formulation.
• Exclusivity_Code & code_meaning : Describes various types of exclusivities granted to certain drugs based on factors such as new chemical formulations/routes/dosage forms/strengths/indications/patient populations/etc., orphan status eligibility & pediatric exclusivity extensions etc
• Trade_Name : Brand name/commercial/marketing name given to each individual pharmaceutical/drug product -Appl_Type : Classification type describing different types of applications submitted to the FDA for a drug; Abbreviated New Drug Applications (ANDAs), New Drug Applications (NDAs) etc -TE_Code: Exclusivity code indicating the type of exclusivity granted to a drug

Understanding this dataset can be helpful in examining and analyzing specific drugs, their manufacturers, patent expiration dates, exclusivities granted by regulatory authorities, and other relevant information. Researchers, pharmaceutical companies, regulators, and healthcare professionals can utilize this dataset to gain insights into the landscape of pharmaceutical drugs listed in the FDA Orange Book as of July 2017

How to use the dataset

Introduction:

• Understanding the Dataset Structure:

  • The dataset consists of three CSV files: patents.csv, reference.csv, and products.csv.
  • Each file contains specific information about pharmaceutical drugs such as patent numbers, expiration dates, applicants' details, dosage forms, trade names, strengths, approval dates, and more.
  • It is important to familiarize yourself with the column names and their corresponding descriptions in order to make proper use of the data.

• Exploring Pharmaceutical Drugs:

  • Start by examining products.csv as it contains detailed information about various drugs.
    • Columns such as Trade_Name provide brand names of the drugs.
    • Strength describes their concentrations or dosages.
    • Applicant_Full_Name indicates the companies or organizations that submitted applications for these drugs.

• Identifying Patent Details:

  • Turn your attention to patents.csv for patent-related information for each drug in the dataset.
    • Patent_No provides unique identification numbers associated with each drug's patent(s).
    • Patent_Expire_Date_Text shows expiration dates of these patents.

• Analyzing Exclusivities:

  • Reference.csv serves as an excellent resource for understanding exclusivity codes used within this dataset.
    • Exclusivity_code represents codes indicating different types of granted exclusivities for specific drugs.
    • For example D stands for New Dosing Schedule while NCE refers to New Chemical entitling 5 years of exclusivity rights Which are available in code_meaning (Description Meaning)

• Cross-referencing Information:

  • The dataset provides several shared columns across the files, such as Appl_No, Product_No, and Ingredient.
  • By cross-referencing these columns, you can link related information between different files and gain a comprehensive understanding of specific drugs.

• Filtering and Sorting Data: ...

Context

International crime is a growing concern, with criminal activities spanning across borders and affecting communities worldwide. Pakistan Today, PS Time and Samma, three leading Pakistani news sources, have been closely monitoring the latest developments in this field. According to their reports, international criminal organizations are becoming more sophisticated and increasingly targeting vulnerable communities. Drug trafficking, human trafficking, and cybercrime are among the most pressing issues facing law enforcement agencies.

Content

"Global Crime on the Rise: The Latest Report from Pakistani News Sources" International crime is a growing concern for communities around the world. In Pakistan, leading news sources such as Pakistan Today, PS Time and Samma have been tracking the latest developments in this field. According to their reports, transnational criminal organizations are becoming more sophisticated and exploiting vulnerable communities, with drug trafficking, human trafficking, and cybercrime being among the most pressing issues. The groups are using technology to carry out their activities, making it more challenging for law enforcement to track them. However, with continued efforts and international cooperation, it is possible to effectively combat these crimes and bring the perpetrators to justice. The public is encouraged to stay informed and report any suspicious activity to the relevant authorities. Stay tuned to Pakistan Today, PS Time, and Samma for the latest updates on the fight against international crime.

Acknowledgement

We would like to acknowledge the valuable contributions made by Pakistan Today, PS Time, and Samma News in collecting and reporting on international crime news. Their tireless efforts in keeping the public informed and updated on these critical issues is greatly appreciated.

Inspiration

1. International crime is a growing concern, but it's important to remember that there is still hope.

2. Pakistani news sources like Pakistan Today, PS Time and Samma are working to shed light on the issue and inspire action.

3. Transnational criminal organizations are becoming more sophisticated and exploiting vulnerable communities.

4. Drug trafficking, human trafficking and cybercrime are among the most pressing issues.

5. Advances in technology have made it more challenging for law enforcement agencies to track criminal activities.

6. The fight against international crime requires international cooperation and continued efforts by law enforcement.

7. The public can play an important role in the fight against international crime by staying informed and reporting suspicious activity.

8. The coverage by Pakistan Today, PS Time, and Samma is raising awareness and inspiring action against these crimes.

9. By working together, we can reduce the harm caused by international crime and make a positive impact in the world.

10.Let's take inspiration from the fight against international crime and work towards a safer, more secure world for all.

Columns detail

Date: Dated

Crimetype: Drug trafficking, human trafficking, cybercrime, and other transnational crimes.

Sourcetype: News articles from leading Pakistani news sources including Pakistan Today, PS Time, and Samma.

Para: International crime is a growing concern, with criminal organizations operating across borders and affecting communities worldwide.