bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of H1N1, H7N9, ASFV, dengue virus and COVID-19 on pharmaceutical manufacturing firms' R&D investments and economic consequences: Evidence from China
Authors: Liu Jie , Zheng Wanqing , Liu Zhen , Jiang Xiujing 
Published: October 2023

Objective:
To determine the impact of major disease epidemics on pharmaceutical manufacturing firms' Research & Development (R&D) investments and economic consequences.

Methods:
The sample consists of 1 582 firm-year observations from 2009 to 2022 in China, of which, 26.6% of pharmaceutical companies are involved in the diagnosis and treatment of prevalent diseases. Linear models using R&D investments, patent applications, operating performances and stock returns as dependent variables are constructed separately to examine the response of pharmaceutical companies to disease epidemics and the resulting economic consequences.

Results:
The prevalence of five major diseases led to a 17.5% increase in the amount of R&D investment and an 87.8% rise in the ratio of R&D investment to total assets by disease-related pharmaceutical companies, compared to unrelated pharmaceutical companies. Further evidence indicated that the patent applications for disease-related firms increased by 44.3% relative to unrelated firms after the epidemics. Though the impacts of the epidemics on firms' operating performances were insignificant in the short term, a major disease epidemic was associated with an increase in stock returns of 67.4% and 44.6%, respectively, as measured by the capital asset pricing model and Fama-French five-factor model. Additional analysis revealed that the impacts of the epidemics on R&D investments and patent applications were more pronounced for non-state-owned enterprises than state-owned enterprises.

Conclusions:
This study demonstrates that disease-related pharmaceutical firms respond to the disease epidemics through increasing R&D investment. More patent applications and higher market value are the main gains from the firms' increased investments in R&D following the epidemic, rather than the improvements of short-term operating performances.
Risk estimation of chronic kidney disease in a leptospirosis endemic area: A case-control study from south Andaman Islands of India
Authors: Fatema Ambreen , Ramu Manjunatha , Vijayachari Paluru 
Published: October 2023

Objective:
To estimate the risk of chronic kidney disease in patients with leptospirosis.

Methods:
All reported (41 890) and later confirmed leptospirosis (1 990) cases from 2010-2020 were traced by universal sampling. 386 Laboratory-confirmed leptospirosis cases were enrolled and 413 age, gender, area, and occupation matched healthy persons were included as controls. Variables including socio-demographic characteristics, medical history, and health-related behaviours were compared between the two groups and association between these variables and reduced estimated glomerular filtration rate (eGFR) was analyzed with multiple linear regression.

Results:
The median of eGFR was 49.0 (27.0, 75.0) mL/min/1.73 m2 in the cases and 96.0 (72.0, 121.0) mL/min/1.73 m2 in the controls, showing significant differences (P <0.001). Bivariate analysis showed that leptospirosis seropositivitiy, repeat leptospirosis infection, diabetes, male gender, working in field (sun exposure), COVID-19 infection and smoking had statistically significant association with reduced eGFR. Leptospirosis seropositivity had negative effects on eGFR. Multiple linear regression confirmed that leptospirosis seropositivity had negative effects on eGFR (unstandardised p coefficients= −30.86, 95% CI −49.7 to −11.9, P <0.001).

Conclusions:
Chronic kidney disease is a complex disease with multiple risk factors involved. Exposure to leptospirosis is one of the essential factors in accelerating its progression.
Investigation of the Test–Retest Reliability and Inter-Rater Agreement of Traditional Chinese Medicine-Based Pulse Diagnosis Among Indian Traditional Chinese Medicine Practitioners
Authors: Jagwani Mamta , Sharma Gita , Sharma Hemanshu , Kafle Tara K. , Tewani Gulab Rai , Nair Pradeep M. K. 
Published: October 2023

Objective:
The objective of this study was to assess the test–retest reliability and inter-rater agreement between the traditional Chinese medicine (TCM) pulse diagnosis between two Indian TCM practitioners.

Methods:
A total of 300 participants were evaluated for their bilateral pulse based on TCM independently by two investigators with similar years of experience but who graduated from different medical schools. The investigators who were blinded diagnosed the participants as per TCM based on the depth, rate, and strength of their pulse. Cronbach α and weighted kappa were used for assessing the reliability and repeatability.

Results:
The data of all the 300 participants were included in the analysis. The test–retest reliability computed using Cronbach’s alpha indicated high reliability between the investigators (α =0.963). There were a total of 37 different types of diagnoses identified by both investigators. The investigators diagnoses matched for 116 participants out of 300 participants; whereas 184 cases were not matched between the investigators. The inter-rater agreement for the TCM diagnosis tested by weighted Kappa did not returned any significant agreement (Kappa = 0.370).

Discussion:
The present study shows higher reliability between the pulse diagnoses between the investigators. However, the inter-rater agreement for TCM diagnosis based on pulse diagnosis was not significant probably due to the variation in subjective assessments. This calls for the standardization of training in TCM diagnostic methods among practitioners. Future studies should include the differences in training, medical education, and experience among the practitioners while determining the reliability of pulse diagnosis.
Effects of Nitric Oxide Supplementation on the Levels of Interleukin-6 in Saliva after Dental Implant Placement - A Prospective Study
Authors: Karabale Nikita , Dhawan Pankaj , Kaur Harsimran , Mahesh Shakila 
Published: October 2023

Abstract

Introduction:
The purpose of the study was to evaluate and compare the levels of salivary Interleukin-6 (IL-6) before and after the placement of dental implants in patients who are supplemented with nitric oxide (NO).

Materials and Methods:
The study comprised 34 patients, divided into control and study groups (17 in each group). The control group was given a placebo and in the study group, nitric oxide supplement was prescribed, whereas the control group received a placebo. Saliva samples were taken before placement of dental implants, first and third day after the implant placement. The levels of salivary IL-6 were assessed using an enzyme-linked immunosorbent assay test.

Results:
Statistical analysis showed a significant P value (<0.05) with respect to IL-6 levels on first and third days after placement of dental implants. Salivary IL-6 levels in the study group declined significantly. On day three, the IL-6 values for the control and study groups were 0.0639 and 0.0443, respectively. Within the groups, it was observed that there was a significant decrease in IL-6 values from day one to day three.

Discussion:
The levels of salivary IL-6 reduced from day one to day three more significantly and consistently in patients prescribed with NO supplements post-dental implant placement, suggesting better resolution of inflammation.
Gestational Diabetes Mellitus – The Modern Indian Perspective
Authors: Rohini H N , Punita Pushpanathan , Santhekadur Prasanna Kumar , Ravishankar MV 
Published: October 2023

Abstract
Gestational diabetes mellitus (GDM) is a serious and most frequent health complication during pregnancy which is associated with a significant increase in the risk of maternal and neonatal outcomes. GDM is usually the result of β-cell dysfunction along with chronic insulin resistance during pregnancy. Seshiah et al. pioneer work led to the adoption of Diabetes in Pregnancy Study Group in India criteria as the norm to diagnose GDM, especially in the community setting. In 2014, the Maternal Health Division of the Ministry of Health and Family Welfare, Government of India, updated guidelines and stressed upon the proper use of guidelines such as using a glucometer for self-monitoring and the use of oral hypoglycaemic agents. The 2018 Government of India guidelines stress the importance of counselling about lifestyle modifications, weight control, exercise, and family planning.
Growth Hormone Cut-Off Post Glucagon Stimulation Test in an Indian Cohort of Overweight/Obese Hypopituitary Patients for the Diagnosis of Adult Growth Hormone Deficiency
Authors: Danda Vijay Sheker Reddy , Kyatham Vivek , Paidipally Srinivas Rao , Bhandiwad Chandrashekar , Palle Sharmila 
Published: October 2023

Abstract
Obesity has been associated with reduced growth hormone (GH) secretion, which might lead to the over diagnosis of adult GH deficiency (GHD) in overweight (OW)/obese hypopituitary patients. Currently, there are no body mass index (BMI)-specific peak GH cut-offs for the glucagon stimulation test (GST) for assessing adult GHD in India, given the BMI cut-offs vary for Asians. The study’s main objective was to determine a peak GH cut-off level for the diagnosis of adult GHD in overweight (OW)/obese individuals utilizing the GST. Forty OW/obese subjects were studied in two groups of 20 each. The first group included 20 OW/obese hypopituitary adults and the second group included 20 control subjects. The intervention consisted of a 3 h GST. The main outcome measured was the peak GH level on GST. The mean age of control subjects was lower (33.15 ± 7.67 v/s. 42.10 ± 13.70 years; P = 0.017) in comparison with hypopituitary adults. The mean BMI (27.93 ± 1.63 v/s. 25.81 ± 1.66 kg/m2; P < 0.001), mean IGF1 (272.81 ± 38.57 v/s. 163.75 ± 42.42; P < 0.001, and mean HOMA IR (11.8 ± 9.7 v/s. 6.02 ± 3.14; P = 0.02) was greater in OW/obese controls. The mean GH peak was significantly higher in control subjects (5.41 ± 3.59 ng/mL v/s. 1.49 ± 1.25 ng/mL; P < 0.001) compared to hypopituitary subjects. ROC curve analysis demonstrated a GH cut-off of 3.3 ng/mL with a moderate sensitivity of 70% and high specificity of 95%, with an AUC of 0.838 (P < 0.001; 95% confidence interval [CI] of 0.710–0.965) for the diagnosis of GHD in overweight/obese hypopituitary adults. This study demonstrates that a cut-off of 3.3 ng/mL would diagnose GHD in Indian overweight/obese hypopituitary adults.
Pilot Study on Gut Microbiota Profile in Indian Children with Type 1 Diabetes
Authors: Shah Nikhil , Kulkarni Abhijit , Mongad Dattatray , Jaani Kunal , Kajale Neha , Tamahane Vaishali , Bhor Shital , Ladkat Dipali , Khadilkar Vaman , Gondhalekar Ketan , Shouche Yogesh , Khadilkar Anuradha V. 
Published: October 2023

Abstract

Background:
Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM).

Objectives:
To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control.

Methodology:
Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis.

Results:
The dominant phyla in children with T1DM were Firmicutes and Bacteroidetes. Butyrate-producing bacteria Blautia and Ruminococcus showed a significant negative correlation with the glycosylated haemoglobin (HbA1C) levels (p < 0.05). Coprococcus and Propionibacterium were important negative predictors of glycaemic control (p < 0.05).

Conclusion:
Our study suggests that Indian children with T1DM have a distinct gut microbiome taxonomic composition and that short-chain fatty acid-producing bacteria like Ruminococcus and Blautia (butyrate-producing) may play an important role in the glycaemic control of subjects with T1DM.
Quantification of Δ9-tetrahydrocannabinol in urine as a marker of cannabis abuse
Authors: Sharma Priyamvada , Rao Vijayashree , Chand Prabhat Kumar , Murthy Pratima 
Published: October 2023

Background & objectives:
Cannabis use has long been associated with celebration and hospitality, although abuse must be confirmed through testing. It has always been difficult to develop an accurate and reliable confirmatory method for the quantification of tetrahydrocannabinol carboxylic acid (THC-COOH) that meets local requirements. The goal was to develop a rapid, cost-effective analytical technique that can handle large batches.

Methods:
Because of the wide metabolite detection window and ease of collection, urine was preferable sample. The extraction of a pre-screened urine sample (adulteration and multidrug screening) was done on Bond Elut cartridges using a positive pressure vacuum manifold, followed by quantification using a gas chromatograph and mass spectrometer.

Results:
The assay was linear between 15 and 300 ng/ml (r

2
of 0.99). The intra-day precision was 8.69 per cent and the inter-day precision was 10.78 per cent, respectively with a 97.5 per cent recovery rate for the lowest concentration. A total of 939 urine samples were examined, with 213 detecting cannabis. Sixty per cent of the total individuals tested positive for simply cannabinoids, 33 per cent for cannabinoids and sedatives, five per cent for cannabinoids and morphine and one for cannabis, morphine and cocaine.

Interpretation & conclusions:
Assay characteristics included modest sample preparation, rapid chromatography, high specificity and small sample volume with a processing time of 12 h. The assay described here can be applied for diagnostic laboratories and in forensic settings as well.
Effectiveness of Lactoferrin in the Treatment of Anemia in Chronic Kidney Disease: A Single-Center Pilot Study
Authors: Kekan Kushal , Divyaveer Smita , Kashyap Madhuri , Premkumar Madhumita , Zohmangaihi Deepy , Mallik Nabhajit , Lad Deepesh , Sharma Akanksha , Gowri Shankar S , Garg Sahil , Prabhahar Arun , Chaudhary Ankur , Suleiman Shabna , Rather Imran , Verma Manish , Jassal Ravjit Singh , Kohli Harbir Singh 
Published: October 2023

Abstract

Background:
Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD).

Methods:
In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks.

Results:
A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: −0.76; 95% confidence interval [CI]: −1.291 to − 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level.

Conclusions:
Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.
ANCA-associated vasculitis with systemic thrombotic microangiopathy: A review of literature
Authors: Shukla Shubham , Sekar Aravind , Naik Sachin , Rathi Manish , Sharma Aman , Nada Ritambhra , Kohli Harbir S. , Ramachandran Raja 
Published: October 2023

Abstract

Introduction:
Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) rarely coexist with systemic thrombotic microangiopathy (TMA). The TMA can be in the form of either hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). This review explores the clinical characteristics, histopathological findings, treatment options, and outcomes in patients presenting as AAV with coexisting HUS/TTP.

Methods:
We conducted a search on the PubMed database and additional searches from January 1998 to September 2022 using the following terms: “ANCA”, “Antineutrophil cytoplasmic antibody”, “thrombotic thrombocytopenic purpura”, “TTP”, “thrombotic microangiopathy”, “haemolytic uremic syndrome”, and “HUS”. We excluded articles that described renal-limited TMA. Two authors independently reviewed the full texts and extracted all critical data from the included case reports. Finally, we included 15 cases for this review. Hematological remission and kidney recovery in the form of independence from dialysis was assessed.

Results:
The median age of the patients was 61 years and a majority of them were females (66.7%). Myeloperoxidase (MPO)-ANCA positivity (66.67%) was more common than proteinase 3 (PR3)-ANCA positivity (33.33%). All patients had laboratory parameters consistent with systemic TMA (HUS or TTP), and only six (out of 11) cases showed histological features of renal TMA. Ten had crescentic glomerulonephritis, and two had advanced degrees of chronicity in histology. Eighty-six percent of cases had hematological remission, and sixty percent of cases became dialysis-independent after treatment.

Conclusion:
In conclusion, kidney outcome was worse in patients who manifested both AAV and systemic TMA. A paucity of literature regarding this diagnostic quandary calls for avid reporting of such cases.
Epidemiology and Risk Factors for Diarrheagenic Escherichia coli Carriage among Children in Northern Ibadan, Nigeria
Authors: Akinlabi Olabisi C. , Nwoko El-shama Q. , Dada Rotimi A. , Ekpo Stella , Omotuyi Adeola , Nwimo Chukwuemeka C. , Adepoju Akinlolu , Popoola Oluwafemi , Dougan Gordon , Thomson Nicholas R. , Okeke Iruka N. 
Published: October 2023

ABSTRACT.
Diarrhea is a leading cause of childhood morbidity in Africa, but few studies, focus on bacterial diarrheal etiology including multicountry studies that typically excluded Nigeria. We collected stool specimens from 477 children under 5 years of age, 120 with diarrhea, who were enrolled in our prospective case-control study between November 2015 and August 2019. All were attending primary health clinics on the northern outskirts of Ibadan. Up to 10 Escherichia coli isolates were obtained per specimen, and at least three of them were sequenced using Illumina whole-genome sequence technology. Genomes were assembled using SPAdes and evaluated for quality using QUAST. VirulenceFinder was used to identify virulence genes. The microbiological quality of water from 14 wells within the study area was assessed using total and coliform counts. Diarrheagenic E. coli (DEC) were isolated from 79 (65.8%) cases and 217 (60.8%) control children. A number of hybrid DEC pathotypes, Salmonella spp., Yersinia spp., and all DEC pathotypes except Shiga toxin-producing E. coli were detected, but no pathogen showed association with disease (P > 0.05). Enterotoxigenic E. coli were more commonly recovered from children without diarrhea aged below 6 months but exclusively detected in children with diarrhea aged over 9 months. Temporally linked, genetically similar enteroaggregative E. coli were isolated from children in different households in eight instances. No well water sample drawn in the study was potable. Children in northern Ibadan were commonly colonized with DEC. Access to water, proper sanitation, and vaccination against the prevailing pathogens may be critical for protecting children from the less overt consequences of enteric pathogen carriage.
¿Qué tan sensibles son los mercados financieros al brote por COVID-19? Evidencia de los mercados de Estados Unidos y Colombia
Authors: Ramírez Quintero James D. , Marulanda Piedrahita Jefferson , Tovar Cuevas José Rafael , Manotas Duque Diego F. 
Published: October 2023

En este artículo, se evalúa el riesgo de mercado asociado a los mercados financieros de New York y Colombia en tres períodos pertenecientes a la ventana temporal 2019-2020, caracterizados por condiciones económicas y sociales impactantes como la guerra de precios del petróleo entre Arabia Saudita y Rusia y la pandemia mundial por COVID-19. Se realiza la medición de riesgo por medio del uso del valor en riesgo (VaR) y déficit medio (MS), aplicando una metodología estadística que considera el uso de técnicas de remuestreo (Bootstrapping) paramétrico y no paramétrico. Se tomaron datos de cinco índices (Standard and Poor’s 500, Dow Jones, COLCAP, VIX y Brent) con el fin de evaluar los efectos ocasionados por variables como el precio del petróleo y las condiciones generadas por la pandemia COVID-19 en las fechas de estudio, como resultado principal se obtiene que en general se presenta una volatilidad muy elevada en los periodos afectados por los dos fenómenos ya mencionados cuando se dieron de manera simultánea, y que además de grandes caídas en los índices de referencia, también se tiene la evidencia de grandes recuperaciones que contribuyen positivamente a la tendencia en los precios.
Indonesian Criminal Code, Living Law and Control in Law Enforcement in Indonesia
Authors: Selajar Sophian Yahya , Martha Aroma Elmina 
Published: October 2023

Introduction: The inclusion of the Living Law concept in the latest Criminal Code as a law that lives in society.Purposes of the Research: This paper analyzes the dialectic of legal certainty according to the principle of legality with living law as the principle of substantive justice in criminal law reform, from the perspective of law as a mechanism of social control and its influence on the dynamics of criminal law enforcement in Indonesia.Methods of the Research: This research uses a normative legal research model. Data collection is done through secondary data searches in the form of primary legal materials and secondary legal materials that are relevant to the object of the problem being studied. The approach used in the analysis is juridical-normative and then elaborated with a sociological approach through social science theories.Results of the Research: The results of the research on the accommodation of living law as a basic principle of criminal law have led to a dialectic between the principle of legal certainty and the principle of substantive justice. Living law is a form of law that is not codified like state law, but rather leads to awareness and cooperation among individuals in a community, so that the function applied is to control over community behavior, so that law enforcement mechanisms run naturally in order to maintain order and public morality.