bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective surveillance study of healthcare-associated infections in an intensive care unit from a tertiary care teaching hospital from 2012–2019
Authors: Li Ruo-Jie , Wu Yi-Le , Huang Kai , Hu Xiao-Qian , Zhang Jing-Jing , Yang Li-Qi , Yang Xi-Yao
Published: August 2023

Healthcare-associated infections (HAIs) continue to be the most common adverse event affecting critically ill inpatients in intensive care units (ICUs). Limited data exist in the English literature on the epidemiology of HAIs in ICUs from China. The purpose of this prospective study was to understand the prevalence and trends of HAIs in the ICU to guide clinicians to take effective prevention and control measures. In total, 20 ICU beds in the hospital from January 2012 to December 2019 were selected for surveillance. HAI diagnosis and device-associated infection surveillance were based on the criteria set forth by the original Ministry of Health of the People’s Republic of China. The full-time staff for HAI management monitored all patients who stayed in the ICU > 48 hours during the study period and calculated the device utilization ratio and device-associated infection rate. The rate of HAIs and the adjusted rate were 18.78 per 1000 patient-days and 5.17 per 1000 patient-days, respectively. The rates of ventilator-associated pneumonias, catheter-associated urinary tract infections, and central line-associated bloodstream infections were 22.68 per 1000 device-days, 2.40 per 1000 device-days, and 2.27 per 1000 device-days, respectively. A total of 731 pathogenic bacteria were detected in the patients with HAIs. Gram-negative and gram-positive bacteria accounted for 67.44% and 16.83%, respectively. Continuous target monitoring, regular analysis of high-risk factors, and timely intervention measures could effectively reduce HAIs in the ICU. Additionally, these findings could be used for developing new strategies to prevent and control HAIs in ICUs.
Researching the molecular mechanisms of Taohong Siwu Decoction in the treatment of varicocele-associated male infertility using network pharmacology and molecular docking: A review
Authors: Wu Bo , Lan Xiaohong , Chen Xuqing , Wu Qinyan , Yang Yang , Wang Yuekun
Published: August 2023

Taohong Siwu Decoction (THSWD) was widely used for the treatment of varicocele-associated male infertility. However, the pharmacological mechanism of action is not completely clear. Therefore, network pharmacology and molecular docking were performed to explore potential mechanism of THSWD in the treatment of varicocele-associated male infertility. The Traditional Chinese Medicine Systems Pharmacology (TCMSP), Swiss Target Prediction, and GeneCards were used to retrieve candidate compounds, action targets, and disease-related targets. The construction of the protein–protein interaction (PPI) network and the screening of core genes were completed by the STRING and Cytoscape 3.9.1, respectively. The DAVID was used to obtain results of gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The Mcule analysis platform was used to perform molecular docking. There were a total of 53 candidate compounds and 782 relevant targets in THSWD. There were 45 common targets between THSWD, varicocele, and male infertility, and 23 core genes were found in the PPI network. Biological processes involved response to hypoxia, regulation of blood pressure, cellular response to hypoxia, and regulation of the nitric oxide biosynthetic process. Furthermore, the KEGG pathway enrichment analysis showed that the common targets mainly regulated the disease of varicocele-associated male infertility through the HIF-1 signaling pathway, PI3K-Akt signaling pathway, Relaxin signaling pathway, and TNF signaling pathway. Finally, the molecular docking showed that luteolin, quercetin, and kaempferol had good intercalation with major targets. As predicted by network pharmacology, THSWD regulated varicocele-associated male infertility through multiple compounds and targets, and its mechanism was closely related to inflammatory response, reactive oxygen species damage, and function of blood vessels.
Early evaluation of waist-to-height ratio for the prediction of worsening acute pancreatitis
Authors: Wang Zhiyang , Xu Yao , Yang Kaijie , Zhou Mengting , Huang Deqiang , Luo Lingyu
Published: August 2023

The purpose of this study was to evaluate the association between the waist-to-height ratio (WHtR) and the aggravation of acute pancreatitis (AP). This prospective study included AP patients treated from May 2019 to December 2019 in the Department of Gastroenterology, the First Affiliated Hospital of Nanchang University. Receiver operating characteristic curves were constructed to determine the optimal threshold values for predicting the aggravation of AP. Risk factor analysis was performed via logistic regression analysis. Of 258 patients included in this study, 77 (29.84%) were diagnosed with mild acute pancreatitis, 120 (46.51%) with moderately severe acute pancreatitis, and 61 (23.64%) with severe acute pancreatitis (SAP). WHtR, waist circumference, weight, and body mass index were all associated with AP severity, and the highest area under the receiver operating characteristic value was observed for WHtR. The optimal threshold WHtR value for predicting SAP was 0.567. Multivariate logistic regression analysis identified WHtR ≥ 0.567 as independent risk factor for SAP. Moreover, the hospital stay was longer and intensive care unit admission rate was higher among AP patients with a WHtR ≥ 0.567. The WHtR was found to be closely related to the severity of AP and an independent risk factor for the aggravation of AP. This simple parameter can aid the early prediction of AP progression, thereby facilitating early intervention and improving patient outcomes.
Efficacy and safety of tralokinumab in the treatment of atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials
Authors: Zhao Dan-Jie , Huang Ling-Mei , Xiao Jie , Chen Long , Li Xia , Lin Hai-Xia
Published: August 2023

Background:

To assess the efficacy and safety of Tralokinumab in the treatment of moderate-to-severe atopic dermatitis (AD).

Methods:

PubMed, Embase, Clinical Trials Website, and Cochrane Library were systematically searched for eligible randomized controlled trials which assessed the effects of Tralokinumab on AD. Primary outcomes included Scoring Atopic Dermatitis score, EASI-75%, and Investigator’s Global Assessment score of 0 or 1 in 12 to 16 weeks. Secondary outcomes included the Eczema area and severity index score, the Numeric Rating Scales score, the dermatology life quality index score, and the overall incidence of adverse events. The quality of included studies was evaluated using the Cochrane System and the modified Jadad scale. Analysis was performed using Stata 16 software.

Results:

Eight randomized controlled trials involving 2878 patients were included in this meta-analysis. Compared to placebo, Tralokinumab treatment exhibited a significantly higher Scoring Atopic Dermatitis score [SMD = −0.53, 95% confidence intervals [CI]: −0.62 to −0.44, P < .00001], an increased number of patients with EASI-75% [odds ratio (OR) = 2.44, 95% CI: 2.00–2.97, P < .00001] and Investigator’s Global Assessment score of 0 or 1 in 12 to 16 weeks [OR = 2.12, 95% CI: 1.71–2.63, P < .00001]. No significant difference was observed in the incidence of overall adverse events [OR = 1.00, 95% CI: 0.85–1.18, P = 1.00] between the 2 groups.

Conclusion:

Tralokinumab is effective and safe in treatment of moderate-to-severe AD.
Current status and progress of laparoscopic inguinal hernia repair: A review
Authors: Xu Li-shuai , Li Qian , Wang Ye , Wang Jia-wei , Wang Song , Wu Cheng-wei , Cao Ting-ting , Xia Ya-bin , Huang Xiao-xu , Xu Li
Published: August 2023

After 30 years of development, laparoscopic inguinal hernia repair (LIHR) has become the main method for treating adult inguinal hernia. LIHR is more standardized, the approach of single-port laparoscopic hernioplasty, the advantages of robotic inguinal hernioplasty, the application of new patches and the selection of surgical methods for different populations have become the focus and difficulty of current research. This article summarized the research progress of LIHR in recent years. Different keywords and phrases including inguinal hernia, LIHR, transabdominal laparoscopic preperitoneal hernia repair, and total extraperitoneal hernia repair were used to search the PubMed, China National Knowledge Infrastructure, and Web of Science databases for related original and review articles that serve the aim of this article well, which was to perform a nonsystematic review of the development, progress, and current status of LIHR.
Efficacy and safety of scalp acupuncture for poststroke depression: A meta-analysis and systematic review
Authors: Jiang Wenxi , Jiang Xicheng , Yu Tianyang , Gao Yang , Sun Yuanzheng
Published: August 2023

Background:

Poststroke depression (PSD) is a common clinical poststroke complication that adversely affects cognitive and physical function rehabilitation. Scalp acupuncture (SA) can significantly improve somatic dysfunction and emotional disorder in stroke patients. This meta-analysis aims to evaluate the effectiveness and safety of SA in the treatment of PSD.

Methods:

We conducted a comprehensive search of multiple electronic databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Internet, China Science and Technology Journal Database, Wan Fang Data Knowledge Service Platform, and China Biology Medicine databases until December 20, 2022, to identify randomized controlled trials investigating the efficacy of SA in the treatment of PSD. Two independent researchers screened the literature, extracted data, and assessed the risk of bias in the included studies based on the inclusion and exclusion criteria. We performed a meta-analysis of the eligible literature using RevMan 5.4.1 and Stata 15.0 software.

Results:

This study comprised a total of 14 randomized controlled trials, 10 of which used SA and 4 of which used SA in combination with electroacupuncture therapy. The results of the meta-analysis revealed that the effective rate of the SA group was significantly higher than that of the Western medicine group (relative risk = 1.09, 95% confidence interval (CI) [1.02, 1.16], P = .008). Moreover, compared to the Western medicine group, the SA group demonstrated significant improvements in Hamilton depression scale scores (mean difference = −2.29, 95% CI [−3.88, −0.70], P = .005) and neurological function deficit scores (mean difference = −3.06, 95% CI [−5.91, −0.21], P = .04). Additionally, the SA group has a lower incidence of adverse events than the western medicine group (relative risk = 0.12, 95% CI [0.05, 0.29], P < .00001).

Conclusion:

SA has superior efficacy and safety compared to Western medicine for PSD. These findings suggest that SA could be a promising alternative treatment for the assessed condition. Due to the limited number and quality of the included literature, the above conclusions must be confirmed by additional high-quality research.
Deep inferior epigastric vessels for free scapular flap phalloplasty
Authors: Li Shuyuan , Luo Sisi , Yang Zhe , Ma Ning , Li Yang-Qun
Published: August 2023

We aimed to present our 20-year experience of using the deep inferior epigastric vessels as recipient vessels for free scapular flaps phalloplasty and evaluate the outcomes. Penile reconstruction was performed using a free scapular flap between 2000 and 2020 by the same surgical team. Deep inferior epigastric vessels were used in all the cases. The surgical techniques and outcomes were described. Overall, 73 patients used the deep inferior epigastric artery (DIEA) as the recipient artery. Regarding the recipient veins, 2 veins were anastomosed in 72 (98.6%) patients, 1 deep inferior epigastric vein (DIEV) was used in 1 patient, 2 DIEV in 14, 1 DIEV + superficial inferior epigastric vein (SIEV) in 13, 1 DIEV + superficial circumflex iliac vein (SCIV) in 38, great saphenous vein (GSV) + SCIV in 4, and GSV + SIEV in 3. The mean age and body mass index of the study cohort was 28 years and 24.3 kg/m2, respectively. The shortest follow-up time was 7 months. Eleven patients had flap-related complications. Three patients were readmitted to the operating room within 24 hours, and 2 of them underwent salvage procedures with venous revision. Two patients lost the entire flap. One patient with 3-cm distal portion necrosis required surgical intervention. Three patients experienced urethral necrosis. DIEA is a suitable receptor artery for inflow. The DIEV, SIEV, and SCIV are available options for venous drainage according to the patient anatomical characteristics. The GSV can be an excellent backup for outflow and salvage procedures.
Diseases caused by floods with a spotlight on the present situation of unprecedented floods in Pakistan: a short communication
Authors: Naeem Aroma , Zaheer Zaofashan , Tabassum Shehroze , Nazir Abubakar , Naeem Farhan
Published: August 2023

Few natural calamities surpass floods in their destructive capabilities. The recent floods in Pakistan were declared the world’s deadliest since the South Asian floods of 2020 and were, by far, the most destructive floods in the country’s history. They have resulted in significant loss of life and property and have served as the harbingers of cutaneous and noncutaneous diseases. These floods have dealt a critical blow to the country’s already struggling healthcare system, which lacks resources for the prompt mobilization of medical personnel and resources to the flood-hit areas. Having lost their houses, the flood victims are wholly exposed to the elements. Lack of access to a clean water supply has predisposed them to a myriad of diseases. We believe that the consolidation of efforts by the national and international community will put an end to the plight of these flood victims. Our article highlights the significant diseases associated with floods, the challenges faced by the flood victims, and recommendations on how their situation can be improved.
The effectiveness of kangaroo mother care in lowering postpartum depression in mothers of preterm and low birth weight babies: a systematic review and meta-analysis
Authors: Anwar Farah , Warsi Arshia , Ahmed Jawad , Zaidi Butool , Turab Areeba , Khan Muhammad A. , Khan Khalid S.
Published: August 2023

Background:

Kangaroo mother care (KMC) intervention involves skin-to-skin contact between mother and infant. Some studies have shown a decrease in postpartum depression (PPD) in mothers of preterm and low birth weight (LBW) infants. However, the literature is scattered and of variable quality.

Aims:

To conduct a systematic review of available literature and provide a comprehensive picture of the effect of KMC on PPD among mothers of preterm and LBW infants.

Methods:

The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. After PROSPERO registration, a systematic search was conducted using PubMed, Cochrane Central Library, and Google Scholar from the inception of the databases till 14 June 2021. Of the 2944 studies assessed for titles and abstracts, nine studies with 2042 participants were included in the review. Included articles targeted mothers with LBW (<2500 g) or preterm infants (<37 weeks), used an authentic PPD tool, and had standard care or an incubator as the control group. Studies not published in English and in which mothers had a previous psychiatric illness were excluded. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized control trials and the Newcastle–Ottawa Scale for observational studies. All the results were converted to standard mean deviation and pooled together using a random-effects model with a 95% CI. A P-value of less than 0.05 is considered significant.

Results:

KMC Intervention was significantly associated with a lower depression score than control groups. The reduction in depression in the intervention (KMC) group was moderate: SMD=−0.38 (−0.68 to −0.08; 95% CI; I
2=86%; P=0.013). No significant difference was found between the PPD scores of both groups using the Edinburgh Postpartum Depression Scale score.

Conclusions:

The authors conclude that the negative effects of LBW and preterm birth experience on maternal mental health can be avoided to a moderate degree by KMC. Due to a lack of methodological uniformity, different scales for outcome measurement, and discrepancies in intervention features, significantly high heterogeneity was detected. The authors need further larger-scale studies with a uniform study design to better predict the efficacy of KMC better.
Effect of cementing technique on aseptic stem loosening in cemented primary total hip arthroplasty: a systematic review and meta-analysis
Authors: Hanif Muhammad , Arshad Naveed , Habib Yasir , Shami Ali Miraj , Rehman Obaid Ur , Rehman Muhammad , Reyaz Muddasir , Mumtaz Hassan
Published: August 2023

Background and objective:

Aseptic stem loosening after total hip arthroplasty surgery is the commonest complication, whether stem is cemented or uncemented. The aseptic cemented stem loosening has been a challenging problem over the years and a leading cause for revision since the inception of total hip arthroplasty. The objective of systematic review and meta-analysis was to determine the impact of cementing technique on aseptic stem loosening in total hip arthroplasty.

Methods:

Cochrane, CINAHL, Embase, Google scholar, Medline, PubMed were searched in 13 December 2020. Two independent investigators extracted the data and a third investigator’s involvement was reached on consensus. A total of 37 studies of revision rate due to aseptic loosening were reviewed by using fixed/random effects size and were grouped by cementing technique and studies’ characteristics. The data were analyzed through Meta-Essentials and RStudio.

Results:

In revision total hip arthroplasty, retained femoral components revisions rate due to aseptic loosening were recorded in 37 studies involving 6167 cases. Aseptic loosening rate collectively was 5.8% (CI 95%, 0.03–0.08) and mean follow-up of study was 12.5 years. The average follow-up period, mean age at index revision surgery and percentage of aseptic loosening were insignificantly associated with revision rate (P≥0.05), in meta-regression univariant analyses.

Conclusion:

This investigative analysis showed that there is a minimal difference between results of cementing techniques of total hip arthroplasty in femoral components in long-term follow-ups, and usually have a low risk of failure.
Use of eradication therapy in adjunction to periodontal therapy versus alone for treatment of Helicobacter pylori infections: a mini review
Authors: Rahat Manahil , Saqib Muhammad , Ahmed Muhammad , Suleman Muhammad , Ismail Syed M. , Mumtaz Hassan , Khalid Hamna
Published: August 2023

Background:

Approximately 50% of the human population on the Earth is estimated to be affected by the bacterium Helicobacter pylori. which causes disease manifestations ranging from peptic ulcer disease to chronic gastritis to gastric cancer. It has been a struggle to contain this bacterium using conventional antibiotics due to rising antimicrobial resistance, which has made its eradication an even bigger challenge. Due to this major issue, scientists have ventured to use alternative approaches to bring about the eradication of H. pylori colonization.

Aim:

The main aim of this review was to update previous studies that investigated periodontal therapy’s effect on H. pylori eradication.

Method:

A systematic electronic search of the currently available research was conducted to identify all the relevant trials and original studies that compared the clinical effect of periodontal therapy in conjunction with eradication therapy.

Results:

The newly updated review of the literature did not change the conclusion previously reached and instead reinforced the fact with more power and more recent studies that the addition of periodontal therapy to eradication therapy for H. pylori is superior to the use of eradication therapy alone for H. pylori.

Core Tip:

The addition of periodontal therapy to the standard eradication therapy may be a clinically viable option and pave the way for tackling the H. pylori burden as well as aiding in the prevention of antimicrobial resistance to an extent, along with immensely increasing the efficacy of the standard eradication therapy for H. pylori that is currently in use around the world.
Hepatitis-E-induced cholestasis in a child: a case report
Authors: Pokhrel Sagar , Bhusal Amrit , Kumari Neelam , Bhattarai Himal Bikram , Banjade Aneeta
Published: August 2023

Introduction and importance:

Hepatitis E virus (HEV) is a major cause of epidemic water-borne hepatitis in tropical and subtropical countries in areas with poor sanitary conditions. The infection by HEV in children is frequent but typically asymptomatic or manifested only as a very mild disease without jaundice, and usually, it often goes undiagnosed. In this case report, the authors describe a case of hepatitis-E-induced cholestasis in a child.

Case presentation:

An 8-year-old male child presented to a Pediatrics emergency with fever and features of acute cholestasis. On abdominal examination, there was non-tender hepatomegaly. The rest of the systemic examinations were normal. Ultrasonography findings were suggestive of acute hepatitis. The liver biopsy report showed hepatic cholestasis and hepatitis. The serological test for hepatitis E IgM was positive. The child was managed symptomatically.

Conclusion:

Although cholestasis is uncommon in children with HEV infection, it should be considered for non-improving clinical status in children with hepatitis. Also, patients with jaundice and Hepatitis E should be followed up by treating physicians until resolution occurs. To the authors’ knowledge, this is the first case report from Nepal describing cholestasis in a child due to HEV infection.
Efficacy and safety of inhaled nitric oxide administered during cardiopulmonary bypass for pediatric cardiac surgery: a systematic review and meta-analysis
Authors: Elnaiem Walaa , Mohamed Elnour Abdulhay , Koko Abubaker E.A. , Madany Maysa , Hemmeda Lina
Published: August 2023

Background and aims:

Cardiopulmonary bypass (CPB) utilized for cardiac surgeries has been associated with significant mortality and adverse outcomes. The benefits of incorporating nitric oxide (NO) into the CPB circuit have been reported in terms of reduced inflammation, enhanced dynamic circulation, oxygenation, and end-organ function. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled NO introduced to the CPB circuit among pediatric patients undergoing various cardiac surgeries.

Methods:

A systematic literature search was conducted on 26 July 2022, using the electronic databases of PubMed, Cochrane, Scopus, and Web of Science to include randomized controlled trials, with no restriction regarding the date of study conduction. The quality of studies was assessed using the Cochrane tool. RevMan 5.3 software was used to analyze data in the inverse variance method, with pooling data as mean difference (MD), risk ratio, and 95% CI.

Results:

Six trials were included comprising 1666 children who had undergone the interventions of interest. All studies amenable to assessment were of good quality. NO was significantly superior to the control treatments regarding ventilation time (MD=−8.34; 95% CI [−14.50 to −2.17], P=0.008), postoperative interleukin-6 (IL-6) levels (MD=−0.50; 95% CI [−0.54 to −0.46], P<0.001), 24-h IL-6 levels (MD=−0.30; 95% CI [−0.32 to −0.20], P<0.001), and 24-h tumor necrosis factor-alpha (TNF-α) levels (MD=−1.72; 95% CI [−3.44 to −1.00], P=0.05). The side effects of NO and the control treatments were comparable (P=0.9).

Conclusion:

NO administered as part of the CPB circuit during cardiac surgeries is efficacious in terms of reducing ventilation time, postoperative IL-6, and TNF-α levels compared to control, with a comparable safety profile.
Prevalence of childhood obstructive sleep apnoea syndrome and its role in daytime sleepiness in Syria: a large-scale school-based cross-sectional study
Authors: Alchallah Mhd Obai , Safiah Mhd Homam , Belah Kajjoun Mohamed Motsem , Kalalib Al Ashabi Khaled , Ataya Sham , Mohsen Fatema , Bakdounes Duaa , ElHomsi Muhammad Omar , Alolabi Homam , Alistwani Dima , Alzein Andrya , Ayash Ahmad , Youzbashi Lamaat , Darjazini Nahas Louei
Published: August 2023

Background:

Obstructive sleep apnoea syndrome (OSAS) has become vastly conceded in the last decade as a possible reason for significant morbidity in childhood. This study aims to evaluate the prevalence of OSAS among school children and to assess the interrelationship between OSAS and daytime sleepiness.

Methods and materials:

This cross-sectional study was conducted with 1029 children and adolescents aged 6–15 years attending elementary and secondary schools in Damascus, Syria. The questions involved 19 sleep problems items using the children sleep habits questionnaire, and 4 sleep disorder items (loud snoring, having snorts or gasps, breathing pauses, daytime sleepiness). Total sleep time (TST) was determined by sleep habits. Severe possible OSAS (p-OSAS) was addressed as having all OSA symptoms “frequently”, and mild p-OSAS was defined as having any of the symptoms “sometimes”. Severe and mild daytime sleepiness were rated as being very sleepy during the day “frequently”, and “sometimes”, respectively. Logistic regression was applied to predict risk factors of severe and mild daytime sleepiness.

Results:

The prevalence of p-OSAS was 22.2%, of them 15.8% were mild, and 6.3% were severe. p-OSAS was more recognized in males 15.2% children (P<0.05). Most p-OSAS children sleep less than 6 h of TST; however; the mean TST was significantly lower at the secondary school level (P≤0.001). Predicted risk factors for severe and mild daytime sleepiness were students’ grade level (P<0.05), severe and mild p-OSAS (P≤0.001), and TST less than 6 h (P≤0.001).

Conclusions:

A significant number of children have p-OSAS, affecting daytime sleepiness in school age. Physicians should consider loud snoring, and breathing pauses as marked symptoms of severe daytime sleepiness. Moreover, raising parents awareness about OSAS and daytime sleepiness is essential to ensure early access to primary care.
Primary gastrointestinal non-Hodgkin lymphoma: a retrospective study in Vietnam
Authors: Tran Thang , Vu Thang Hong , Vo Hoan Quoc , Thi Nguyen Hoa , Van Nguyen Hung
Published: August 2023

Background:

Although primary gastrointestinal non-Hodgkin lymphoma (GI NHL) is a rare hematopoietic malignancy, it is the most common extranodal site involved by lymphoma. Treatment methods are chosen based on many factors, including site of lesion, histopathology, symptoms, and patients’ choice.

Objectives:

To evaluate the clinical characteristics, treatment results and prognosis for primary GI NHL in Vietnamese patients.

Patients and methods:

This was a retrospective descriptive study on 126 patients with primary GI NHL treated at our hospital from 2010 to 2015. Data of all patients were collected and analyzed.

Results:

B-cell non-Hodgkin’s lymphoma was the major pathology with rate of 93.7%, in which Diffuse Large B-Cell Lymphoma type accounted for 58.7%, followed by Mucosa-associated lymphoid tissue lymphoma type 22.2%. Less common forms were cystic type, Burkitt’s lymphoma, Mantle cell, T cell. The majority of patients receiving chemotherapy achieved a complete response, up to 70%. Overall survival and 5-year disease-free survival were 74.1% and 59.3%, respectively. Overall, stomach lymphoma had a longer survival rate than those in the small intestine. Factors including Eastern Cooperative Oncology Group score of 2–4, elevated Lactate Dehydrogenase levels at baseline, stage of widespread illness (III/IV), high malignancy histopathology, and lesion size of more than 10 cm were poor prognostic indicators.

Conclusions:

Gastric lesion was the most frequent site and has better prognosis than other locations. Other prognostic factors for overall survival included Eastern Cooperative Oncology Group score, Lactate Dehydrogenase levels, stage, histopathology, and lesion size.
Utility of Serum Amylase in Children With Abdominal Pain in the Pediatric Emergency Department
Authors: Friend Rachel , Hash David , Rivera-Sepulveda Andrea
Published: August 2023

Objectives

Abdominal pain is among the most common chief complaints seen in pediatric emergency departments (PEDs). This study aims to evaluate the diagnostic utility of amylase and lipase in the evaluation of abdominal pain in the PED.

Methods

Retrospective, cross-sectional study of patients aged 0 to 18 years with amylase and/or lipase while in the PED in 2019. Diagnostic utility of amylase and lipase was analyzed with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). The χ2 or Fisher exact test was used when appropriate.

Results

We identified 496 PED visits with tests for amylase (0.2%), lipase (53%), or both (46.8%). Abnormal levels for amylase and lipase were 4.6% and 5.6%, respectively. Amylase use in abdominal pain evaluation showed sensitivity of 30%, specificity of 92%, PPV of 26%, NPV of 93%, and LR of 7.1 (P = 0.008). Lipase use in abdominal pain evaluation showed sensitivity of 7.5%, specificity of 94.5%, PPV of 10.7%, NPV of 92%, and LR of 0.251 (P = 0.616). Amylase at 3 times its normal level showed sensitivity of 10%, specificity of 99.5%, PPV of 66.7%, NPV of 92.2%, and LR of 6.35 (P = 0.012), whereas lipase showed a sensitivity of 5%, specificity of 99.3%, PPV of 40%, NPV of 92.2%, and LR of 3.9 (P = 0.048). Identification of a clinically significant diagnosis via coordering of amylase and lipase versus lipase alone was not significant.

Conclusions

Although serum amylase and lipase testing may be suitable for abdominal pain screening, the concurrent use of both does not seem to add any clinically significant value to diagnosis.
Quantifying stochastic establishment of mutants in microbial adaptation
Authors: Alexander Helen K.
Published: August 2023

Studies of microbial evolution, especially in applied contexts, have focused on the role of selection in shaping predictable, adaptive responses to the environment. However, chance events – the appearance of novel genetic variants and their establishment, i.e. outgrowth from a single cell to a sizeable population – also play critical initiating roles in adaptation. Stochasticity in establishment has received little attention in microbiology, potentially due to lack of awareness as well as practical challenges in quantification. However, methods for high-replicate culturing, mutant labelling and detection, and statistical inference now make it feasible to experimentally quantify the establishment probability of specific adaptive genotypes. I review methods that have emerged over the past decade, including experimental design and mathematical formulas to estimate establishment probability from data. Quantifying establishment in further biological settings and comparing empirical estimates to theoretical predictions represent exciting future directions. More broadly, recognition that adaptive genotypes may be stochastically lost while rare is significant both for interpreting common lab assays and for designing interventions to promote or inhibit microbial evolution.
A dose-finding study to guide use of verapamil as an adjunctive therapy in tuberculosis
Authors: Padmapriyadarsini Chandrasekaran , Szumowski John D. , Akbar Nabila , Shanmugasundaram Prema , Jain Anilkumar , Bathragiri Marasamy , Pattnaik Manoranjan , Turuk Jyotirmayee , Karunaianantham Ramesh , Balakrishnan Senthilkumar , Pati Sangamitra , Agibothu Kupparam Hemanth K. , Rathore Manoj Kumar , Raja Jegadeesh , Raghu Naidu K. , Horn John , Whitworth Laura , Sewell Roger , Ramakrishnan Lalita , Swaminathan Soumya , Edelstein Paul H.
Published: August 2023

Induction of mycobacterial efflux pumps is a cause ofMycobacterium tuberculosis(Mtb) drug tolerance, a barrier to shortening antitubercular treatment. Verapamil inhibits Mtb efflux pumps that mediate tolerance to rifampin, a cornerstone of tuberculosis treatment. Verapamil’s mycobacterial efflux pump inhibition also limits Mtb growth in macrophages in the absence of antibiotic treatment. These findings suggest that verapamil could be used as an adjunctive therapy for TB treatment shortening. However, verapamil is rapidly and substantially metabolized when co-administered with rifampin. We determined in a dose-escalation clinical trial that rifampin-induced clearance of verapamil can be countered without toxicity by the administration of larger than usual doses of verapamil. An oral dosage of 360 mg sustained-release (SR) verapamil given every 12 hours concomitantly with rifampin achieved median verapamil exposures of 903.1 ng.h/ml (AUC 0-12h), similar to those in persons receiving daily doses of 240 mg verapamil SR but not rifampin. Norverapamil:verapamil, R:S verapamil and R:S norverapamil AUC ratios were all significantly greater than those of historical controls receiving SR verapamil in the absence of rifampin, suggesting that rifampin administration favors the less-cardioactive verapamil metabolites and enantiomers. Finally, rifampin exposures were significantly greater after verapamil administration. Our findings suggest that a higher dosage of verapamil can be safely used as adjunctive treatment in rifampin-containing treatment regimens.
A Cross-Sectional Analysis of Syncytiotrophoblast Membrane Extracellular Vesicles Derived Transcriptomic Biomarkers in Preeclampsia
Authors: Awoyemi Toluwalase , Zhang Wei , Rahbar Maryam , Cribbs Adam , Logenthiran Prasanna , Jiang Shuhan , Collett Gavin , Cerdeira Ana Sofia , Vatish Manu
Published: August 2023

Background

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2-8% of pregnancies worldwide. Biomarker(s) for PE exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles - STB-EVs-have been identified as being involved in PE with the potential to act as liquid biopsies.

Objective

To identify differences in STB-EV and placenta transcriptome between PE and normal pregnancy (NP).

Methods

We performed RNA-sequencing (RNA-seq) on placental tissue, medium/large and small STB-EVs from PE (n=6) and NP (n=6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions.

Results

Our analysis identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in-silico prediction of STB-EV-based mechanistic pathways.

Conclusions

In this study, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies.

Funding

This research was funded by the Medical Research Council (MRC Programme Grant (MR/J0033601) and the Medical & Life Sciences translational fund (BRR00142 HE01.01)
Passive sensing data predicts stress in university students: A supervised machine learning method for digital phenotyping
Authors: Shvetcov Artur , Kupper Joost Funke , Zheng Wu-Yi , Slade Aimy , Han Jin , Whitton Alexis , Spoelma Michael , Hoon Leonard , Mouzakis Kon , Vasa Rajesh , Gupta Sunil , Venkatesh Svetha , Newby Jill , Christensen Helen
Published: August 2023

University students are particularly susceptible to developing high levels of stress, which occur when environmental demands outweigh an individual’s ability to cope. The growing advent of mental health smartphone apps has led to a surge in use by university students seeking ways to help them cope with stress. Use of these apps has afforded researchers the unique ability to collect extensive amounts of passive sensing data including GPS and step detection. Despite this, little is known about the relationship between passive sensing data and stress. Further, there are no established methodologies or tools to predict stress from passive sensing data in this group. In this study, we establish a clear machine learning-based methodological pipeline for processing passive sensing data and extracting features that may be relevant in the context of mental health. We then use this methodology to determine the relationship between passive sensing data and stress in university students. In doing so, we offer the first proof-of-principle data for the utility of our methodological pipeline and highlight that passive sensing data can indeed digitally phenotype stress in university students.
Characterization of an extreme phenotype of schizophrenia among women with homelessness
Authors: Menon Jayakumar , Kantipudi Suvarna Jyothi , Mani Aruna , Radhakrishnan Rajiv
Published: August 2023

Background

Studies of schizophrenia and homelessness are often confounded by comorbid substance use. Women with schizophrenia and homelessness in India have very low rates of substance use and provide a unique opportunity to disentangle the effects of illness from that of substance use. We examined the clinical characteristics of women with schizophrenia and homelessness and compared it to an age-matched group of women with schizophrenia living with their family.

Methods

36 women with schizophrenia and homelessness, and 32 women with schizophrenia who were illness living with family were evaluated for psychopathology using Scale for Assessment of Positive Symptoms (SAPS)/ Scale for assessment of negative symptoms (SANS) scales, cognitive difficulties using Montreal Cognitive Assessment (MOCA)/Rowland Universal Dementia Scale (RUDAS), and Frontal Assessment Battery(FAB), disability using World Health Organization - Disability assessment Scale (WHO-DAS) and psychosocial factors using a semi-structured proforma. The groups were compared using t-tests and chi-square for continuous and categorical variables respectively.

Results

Women with schizophrenia and homelessness were found to have significantly higher scores on measures of psychopathology, significantly lower cognitive functioning, and much higher disability, and were also on higher doses of antipsychotics. The mean scores on measures of psychopathology, cognition and disability for women with schizophrenia and homelessness differed by 2-3 standard deviations with the mean for women living with family (i.e. z scores) suggesting that they represented an extreme phenotype. Rates of past employment were higher among women with schizophrenia and homelessness. Hence these differences were not accounted for by premorbid functioning.

Conclusions

The study raises the possibility of an extreme phenotype of schizophrenia with severe and persistent psychopathology non-responsive to dopamine blocking drugs, cognitive impairment, and disability, which needs further exploration.
Integration of polygenic and gut metagenomic risk prediction for common diseases
Authors: Liu Yang , Ritchie Scott , Teo Shu Mei , Ruuskanen Matti Olavi , Kambur Oleg , Zhu Qiyun , Sanders Jon , Vazquez-Baeza Yoshiki , Verspoor Karin , Jousilahti Pekka , Lahti Leo , Niiranen Teemu , Salomaa Veikko , Havulinna Aki , Knight Rob , Méric Guillaume , Inouye Michael
Published: August 2023

Multi-omics has opened new avenues for non-invasive risk profiling and early detection of complex diseases. Both polygenic risk scores (PRSs) and the human microbiome have shown promise in improving risk assessment of various common diseases. Here, in a prospective population-based cohort (FINRISK 2002; n=5,676) with ∼18 years of e-health record follow-up, we assess the incremental and combined value of PRSs and gut metagenomic sequencing as compared to conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer’s disease (AD) and prostate cancer. We found that PRSs improved predictive capacity over conventional risk factors for all diseases (ΔC-indices between 0.010 – 0.027). In sex-stratified analyses, gut metagenomics improved predictive capacity over baseline age for CAD, T2D and prostate cancer; however, improvement over all conventional risk factors was only observed for T2D (ΔC-index 0.004) and prostate cancer (ΔC-index 0.005). Integrated risk models of PRSs, gut metagenomic scores and conventional risk factors achieved the highest predictive performance for all diseases studied as compared to models based on conventional risk factors alone. We make our integrated risk models available for the wider research community. This study demonstrates that integrated PRS and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.
LLIN Evaluation in Uganda Project (LLINEUP) –Plasmodiuminfection prevalence and genotypic markers of insecticide resistance inAnophelesvectors from 48 districts of Uganda
Authors: Lynd Amy , Gonahasa Samuel , Staedke Sarah G , Oruni Ambrose , Maiteki-Sebuguzi Catherine , Hancock Penny , Knight Erin , Dorsey Grant , Opigo Jimmy , Yeka Adoke , Katureebe Agaba , Kyohere Mary , Hemingway Janet , Kamya Moses R , McDermott Daniel , Lucas Eric R. , Donnelly Martin J
Published: August 2023

Background

In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus the synergist piperonyl butoxide (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, cross-sectional entomological surveys were carried out at baseline and then every 6 months for two years. In each survey, ten households per HSD were randomly selected for indoor household entomological collections.

Results

Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected withPlasmodium falciparumdid not change significantly over time, while infection with non-falciparummalaria decreased inAn. gambiaes.s, but notAn. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutationVgsc-995S declined over time asVgsc-995F, the alternative resistance mutation at this codon, increased.Vgsc-995F appears to be spreading into Uganda.

Conclusions

Distribution of LLINs in Uganda was associated with reductions in parasite prevalence and vector density, but the proportion of infective mosquitoes remained stable, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.

Trial registration: This study is registered with ISRCTN,ISRCTN17516395. Registered 14 February 2017,http://www.isrctn.com/ISRCTN17516395
Racial/Ethnic Differences in COVID-19-Traumatic Symptoms, Sleep, Coping Outcomes in a Group of New-Yorkers
Authors: Blanc Judite , Seixas Azizi , Small Sean , Auguste Evan , Briggs Anthony , Antoine Yoann Sophie , Bubu Omonigho Michael , Jean-Louis Girardin
Published: August 2023

Background

Little research has examined within/between group predictors and mediators of race/ethnic differences or disparities in mental and sleep health outcomes arising from the experience of the COVID-19 pandemic.

Objectives

This study sought to evaluate the effect of COVID-19 experiences on trauma-related symptoms and sleep quality among a multiracial/ethnic sample in New York.

Method

This is a cross-sectional study conducted online among multiethnic adults (n=541) who experienced the pandemic in New York from September to November 2020. Comparisons of characteristics and mean scores by race/ethnicity status were conducted using one-way ANOVA and independent samples t-tests for continuous variables and chi-square tests for categorical variables. Multilinear regression was used for associations between social determinants of health and/or SES, trauma-related symptoms, coping, and sleep.

Results

Compared to Whites [Mean (SD)= (24.1(7.6)] and other group [Mean (SD)=24.9(8.2), Blacks [Mean (SD)=(26.3(6.4)] and Hispanics [Mean(SD)=(27.2(8.2)] reported higher level of peritraumatic distress [df= 3; F=4273; p=0.005). The prevalence of clinically significant PTSD symptoms was 21.4%(n=113): [Whites=31(16.3%); Blacks=28(25.7%); Hispanics=24(25%); and other groups=30(22.4%); x2 =4.93; p=0.177]. This rate doubled [48.3%(257)] when it comes to the overall clinically significant depression level. Compared to all subcategories, [Blacks=52(47.7%); Hispanics =62(64.6%); other group=66(49.3%)], depression symptoms were lower among Whites [77(39.9%;x2 =15.71;p=0.001]. We found a prevalence of insufficient sleep <6 hours of 41%(198): [Whites=69(39.4%); Blacks=43(41.7%); Hispanics=46(52.3%); other groups=40(34.2%);x2=12.21;p=0.057]. Several unique demographic predictors of PTSD emerged for distinct racial/ethnic groups. Among Blacks, sex [β = −0.22; p < .01] and employment [β = −0.159; p < .05] emerged as significant predictors for PTSD, but for no other racial/ethnic group. Interestingly, among Hispanics [β = −0.144; p = .064] and Blacks [β = −0.174; p = .0.076], coping strategies did not mitigate PTSD or depressive symptoms.

Conclusion

As New York and the rest of the world are trying to bounce back from the COVID-19 consequences, mental health outcomes are devastating, particularly among historically marginalized communities. This study provides insight into the emergency for policymakers to invest in racial justice programs and provide free access to culturally responsive mental health care for the most vulnerable groups.
Molecular pharmacology of selective Nav1.6 and dual Nav1.6 and Nav1.2 channel inhibitors that suppress excitatory neuronal activity ex vivo
Authors: Goodchild Samuel J. , Shuart Noah Gregory , Williams Aaron D. , Ye Wenlei , Parrish R. Ryley , Soriano Maegan , Thouta Samrat , Mezeyova Janette , Waldbrook Matthew , Dean Richard A. , Focken Thilo , Ghovanloo Mohammad-Reza , Ruben Peter C. , Scott Fiona , Cohen Charles J. , Empfield James R. , Johnson JP
Published: August 2023

Sodium channel inhibitors are used to treat neurological disorders of hyperexcitability. However, all currently available sodium channel targeting anti-seizure medications are non-selective among the NaVisoforms which potentially limits efficacy and therapeutic safety margins. XPC-7724 and XPC-5462 represent a new class of small molecule compounds. These compounds target inhibition of the NaV1.6 and NaV1.2 channels in excitatory pyramidal neurons and possess a molecular selectivity of >100 fold against NaV1.1 channels that are dominant in inhibitory cells. This profile will enable pharmacological dissection of the physiological roles of NaV1.2 and NaV1.6 and help to define the role of each channel in disease states. These compounds bind to and stabilize the inactivated-state of the channels, demonstrate higher potency with longer residency times, and slower off-rates than carbamazepine and phenytoin. These compounds possess cellular selectivity ex vivo in inhibiting action potential firing in cortical excitatory pyramidal neurons, whilst sparing fast spiking inhibitory interneurons. XPC-5462 also suppresses epileptiform activity in an ex vivo brain slice seizure model. This class of compounds provides a unique approach for treating neuronal excitability disorders by selectively down-regulating excitatory circuits.

Graphical Abstract