bluuebunny/crossref_metadata_2025 huggingface dataset:
HEMIN ATTENUATED LPS-INDUCED ACUTE LUNG INJURY IN MICE VIA PROTECTING PULMONARY EPITHELIAL BARRIER AND REGULATING HO-1/NLRP3-MEDIATED PYROPTOSIS
Authors: Cheng Xue , Yin Mingzhu , Sun Xiongjie , Zhang Zhigang , Yao Xiaowei , Liu Hongtao , Xia Hui
Published: February 2023

Pulmonary epithelial barrier injury contributes to acute lung injury, accelerating exudate formation, and resulting alveolar edema. Heme oxygenase-1 (HO-1) plays an important role in ameliorating the pathological symptoms of acute lung injury (ALI). Using an ALI mouse model induced by LPS inhalation, the present study explored the potential molecular regulatory effect of hemin (a potent HO-1 inducer) against ALI epithelial damage. Lipopolysaccharide challenge triggered dysfunction of the alveolar epithelial barrier, impaired tight junctions, and disrupted alveoli fluid clearance, while these pathological changes were effectively reversed by hemin treatment. Furthermore, HO-1 elevation inhibited the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome and oxidative stress in alveolar epithelia, leading to the suppression of inflammatory responses and epithelial pyroptosis, as indicated by the decreased levels of NLRP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC), repressed cleavage of caspase-1 and gasdermin D, and reduced expression levels of inflammatory cytokine IL-1β. In contrast, protoporphyrin IX zinc (II) (ZnPP, an HO-1 inhibitor) treatment had no protective effect on LPS inhalation-induced ALI in mice. In summary, HO-1 induction serves a critical role in maintaining airway epithelium homeostasis through the inhibition of NLRP3/ASC/caspase-1–mediated pyroptosis and inflammation in the occurrence of ALI.
Fully Covered Metal Stents Safely Facilitate Extraction of Difficult Bile Duct Stones
Authors: Koksal Aydin Seref , Eminler Ahmet Tarik , Parlak Erkan
Published: February 2023

Background:

Ten to 15% of the common bile duct (CBD) stones require advanced endoscopic extraction techniques during endoscopic retrograde cholangiopancreatography. The study aimed to evaluate the efficacy and safety of fully covered self-expandable metal stents (FC-SEMS) for facilitating the extraction of difficult bile duct stones.

Methods:

Patients who received FC-SEMS for the extraction of difficult CBD stones were retrospectively reviewed. Group 1 included patients with extrahepatic stones above a distal CBD stricture, Group 2 included patients with intrahepatic stones above a hilar stricture, and Group 3 included patients with complex stone(s) and no biliary stricture. Complete stone clearance rate and complications of FC-SEMS treatment were evaluated.

Results:

The study group included 33 procedures on 32 patients (mean age: 55±17, 56.3% male). FC-SEMS was placed as a primary treatment in 15 (45.5%) procedures. Complete stone clearance was achieved in 84.6% of the procedures in Group 1, 100% in Group 2, and 87.5% in Group 3 (P=0.23). Overall, complete stone clearance was achieved in 30 of the 33 procedures (90.9%). None of the patients developed pancreatitis, cholecystitis, or cholangitis. Stent migration occurred in 4 procedures (12.1%), and all were clinically insignificant.

Conclusion:

FC-SEMS is effective and safe for facilitating treatment of difficult bile duct stones.
Secure Robotic Transthoracic Valvuloplastic Esophagogastrostomy by Double Flap Technique in Esophagogastric Junctional Cancer Surgery
Authors: Noshiro Hirokazu , Manabe Tatsuya , Yoda Yukie , Tsuru Yasuhiro
Published: February 2023

Valvuloplastic esophagogastrostomy by the double flap technique (VPEG-DFT) after proximal gastrectomy for early proximal gastric cancer or esophagogastric junctional cancer (EGJC) is a promising procedure to prevent reflux. However, the transhiatal procedure alone for alimentary reconstruction is sometimes too complex because of the short esophageal remnant. Therefore, additional transthoracic procedures are needed in some patients with EGJC. Although additional thoracoscopic surgery has been reported, no reports to date have described robotic transthoracic VPEG-DFT after excision of EGJC. We herein describe the secure robotic techniques of transthoracic VPEG-DFT performed in 3 patients with EGJC. After completion of the abdominal procedures by robotic and extracorporeal creation of H-shaped flaps on the gastric remnant, robotic VPEG-DFT through the right thoracic approach was performed in the prone position. To accomplish VPEG-DFT in the thorax of patients in the prone position, fixation of the esophagus and stomach was performed before the rotation of the 2 organs to expose the planned anastomotic aspect. In addition, the final abdominal phase was required again to prevent a postoperative hiatal hernia. Secure techniques of right transthoracic VPEG-DFT by robotic surgery could contribute to the successful treatment of EGJC when the remnant esophagus is too short.
Efficacy of Reinforced Stapler Versus Hand-sewn Closure of the Pancreatic Stump During Pure Laparoscopic Distal Pancreatectomy to Reduce Pancreatic Fistula
Authors: Murata Yasuhiro , Maeda Koki , Ito Takahiro , Gyoten Kazuyuki , Hayasaki Aoi , Iizawa Yusuke , Fujii Takehiro , Tanemura Akihiro , Kuriyama Naohisa , Kishiwada Masashi , Mizuno Shugo
Published: February 2023

Background:

Laparoscopic distal pancreatectomy (L-DP) is the standard procedure for treating left-sided pancreatic tumors. Stapler closure of the pancreas is the preferred method for L-DP; however, postoperative pancreatic fistula (POPF) remains a challenging problem. The present study aimed to compare the surgical outcomes of staple closure using a reinforcing stapler (RS) and transection using an ultrasonic dissector followed by hand-sewn (HS) closure in a fish-mouth manner in pure L-DP and to determine independent perioperative risk factors for clinically relevant postoperative pancreatic fistula (CR-POPF).

Patients and Methods:

Among the 85 patients who underwent pure L-DP between February 2011 and August 2021, 80 of whom the pancreatic stump was closed with RS (n = 59) or HS (n = 21) were retrospectively investigated. Associations between potential risk factors and POPF were assessed using univariate analysis. The factors, of which the P value was determined to be <0.1 by univariate analysis, were entered into a multivariate regression analysis to ascertain independent predictive factors.

Results:

The surgery time and estimated blood loss were not significantly different between the two groups. Overall, 13 patients (16.3%) developed CR-POPF (B = 12 and C = 1). The rate of CR-POPF was lower in RS than in HS; however, the difference was not statistically significant (RS vs HS: 11.9% vs 28.9%, P = 0.092). Consistent with the results for CR-POPF, the rate of Clavien-Dindo IIIa or more postoperative complications and the length of hospital stay were also not significantly different between the two groups (RS vs HS: 10.2, 12% vs 14.3%, 14 d). In the univariate analysis of risk factors for CR-POPF, the pancreatic thickness at the transection site, procedure for stump closure, and estimated blood loss were associated with a significantly higher rate of CR-POPF. The multivariate analysis revealed that the pancreatic thickness at the transection site (cutoff: 12 mm) was the only independent risk factor for CR-POPF (odds ratio: 6.5l, 95% CI: 1.4-30.4, P = 0.018). The rate of CR-POPF was much lower in RS than in HS for pancreatic thickness <12 mm (RS vs HS: 4.1% vs 28.6%), whereas that was rather higher in RS than in HS for pancreatic thickness ≥12 mm (RS vs HS: 50% vs 28.6%).

Conclusions:

RS closure was superior to HS closure for pancreatic thickness <12 mm and for prevention of CR-POPF after pure L-DP. It is necessary to seek more reliable procedures for pancreatic stump closure in patients with a pancreatic thickness of ≥12 mm.
Timing of Bariatric Surgery and COVID-19 Vaccination: Experience From a High-volume Single Center
Authors: Vitiello Antonio , Berardi Giovanna , Velotti Nunzio , Schiavone Vincenzo , Abu-Abeid Adam , Musella Mario
Published: February 2023

Background:

During the last year, there was a large COVID-19 vaccination campaign in Italy. Concurrently, metabolic bariatric surgery (MBS) restarted after a long period of discontinuity. No data are currently available on the best timing of COVID-19 vaccination for MBS candidates. The aim of this study was to report MBS outcomes in relation to the timing of COVID-19 vaccine administration.

Materials and Methods:

A prospectively maintained database was utilized to locate patients undergoing MBS between January 1 and December 31, 2021. Patients were divided into 2 groups: patients receiving a vaccine dose within 30 days before or after surgery (Group±30); and patients with a longer time interval of vaccine dose before or after surgery (Group>±30). Postoperative outcomes were recorded and compared.

Results:

A total of 108 patients were included: 33 (30.6%) of whom were in Group±30 and 74(69.4%) in Group>30. Baseline characteristics were comparable between the 2 groups. Findings revealed that postoperative outcomes (ie, 30-d complications and length of stay postoperatively) were comparable between groups. Two patients in the ±30 group had mesenteric vein thrombosis after sleeve gastrectomy (SG); however, the rate of thrombosis events was comparable between groups (P=0.09). Thrombosis between SG patients were not significantly different between the 2 groups.

Conclusions:

COVID-19 vaccination within 30 days of MBS does not impact complication rates and length of stay. COVID-19 vaccination may have a negative impact on venous thrombosis after SG, but this study is underpowered to draw this conclusion. Larger studies should be conducted to replicate current study findings.
Minimally Invasive Surgery for the Treatment of Moderate to Critical Acute Pancreatitis: A Case-matched Comparison With the Traditional Open Approach Over 10 years
Authors: Morelli Luca , Guadagni Simone , Palmeri Matteo , Bechini Bianca , Gianardi Desirée , Furbetta Niccolò , Di Franco Gregorio , Di Candio Giulio
Published: February 2023

Purpose:

The purpose of this study is to compare short-term and midterm outcomes between patients with acute pancreatitis (AP) treated with minimally invasive surgery (MIS) and patients treated with open necrosectomy (ON).

Materials and Methods:

We compared data of all patients who had undergone MIS for AP with a similar group of patients with ON patients between January 2012 and June 2021 using a case-matched methodology based on AP severity and patient characteristics. Inhospital and midterm follow-up variables, including quality-of-life assessment, were evaluated.

Results:

Starting from a whole series of 79 patients with moderate to critical AP admitted to our referral center, the final study sample consisted of 24 patients (12 MIS and 12 ON). Postoperative (18.7±10.9 vs. 30.3±21.7 d; P=0.05) and overall hospitalization (56.3±17.4 vs. 76.9±39.4 d; P=0.05) were lower in the MIS group. Moreover, the Short-Form 36 scores in the ON group were statistically significantly lower in role limitations because of emotional problems (P=0.002) and health changes (P=0.03) at 3 and 6 months and because of emotional problems (P=0.05), emotional well-being (P=0.02), and general health (P=0.007) at 1 year.

Conclusions:

MIS for the surgical management of moderate to critical AP seems to be a good option, as it could provide more chances for a better midterm quality of life compared with ON. Further studies are needed to confirm our findings.
Characterization of Balance Control and Postural Stability in Patients With Alzheimer Disease
Authors: So Raymond J. , Biju Kevin , Oh Esther , Rosenberg Paul , Xue Qian-Li , Dash Paul , Burhanullah Muhammad H. , Agrawal Yuri
Published: February 2023

Balance in Alzheimer disease (AD) patients is not rigorously understood. In this study, we characterize balance using qualitative [Berg Balance Scale (BBS)] and quantitative measures (posturography) and assess relationships between qualitative and quantitative balance measures in AD. Patients with mild-moderate AD (n=48) were recruited. BBS scores and posturography metrics, including medial-lateral sway range, anterior-posterior sway range, sway area, and sway velocity, were assessed in eyes-open and eyes-closed conditions. Adjusted linear regressions were used to assess relationships between posturography and BBS score. Mean BBS score was 50.4±5.3. In eyes-open conditions, posturography and BBS score were not significantly associated. In eyes-closed conditions, better BBS score was significantly associated with lower sway area (β=−0.91; P=0.006). Better scores of BBS items involving turning and reduced base of support were associated with greater eyes-closed sway area. Posturography in the more challenging eyes-closed condition may predict functional balance deficits in AD patients.
Assessing the evolution of SARS-CoV-2 lineages and the dynamic associations between nucleotide variations
Authors: Gupta Asmita , Basu Reelina , Bashyam Murali Dharan
Published: February 2023

Despite seminal advances towards understanding the infection mechanism of SARS-CoV-2, it continues to cause significant morbidity and mortality worldwide. Though mass immunization programs have been implemented in several countries, the viral transmission cycle has shown a continuous progression in the form of multiple waves. A constant change in the frequencies of dominant viral lineages, arising from the accumulation of nucleotide variations (NVs) through favourable selection, is understandably expected to be a major determinant of disease severity and possible vaccine escape. Indeed, worldwide efforts have been initiated to identify specific virus lineage(s) and/or NVs that may cause a severe clinical presentation or facilitate vaccination breakthrough. Since host genetics is expected to play a major role in shaping virus evolution, it is imperative to study role of genome-wide SARS-CoV-2 NVs across various populations. In the current study, we analysed the whole genome sequence of 3543 SARS-CoV-2 infected samples obtained from the state of Telangana, India (including 210 from our previous study), collected over an extended period from April, 2020 to October, 2021. We present a unique perspective on the evolution of prevalent virus lineages and NVs during this time period. We also highlight presence of specific NVs likely to be associated favourably with samples classified as vaccination breakthroughs. Finally, we report genome-wide intra-host variations (iSNVs) at novel genomic positions. The results presented here provide critical insights into virus evolution over an extended time period and pave the way to rigorously investigate the role of specific NVs in vaccination breakthroughs.
Radiobacillus kanasensis sp. nov., a halotolerant bacterium isolated from woodland soil
Authors: Zhang Lijuan , Huang Wei , Ning Wang , Song Bo , Osman Ghenijan , Zhu Jing , Wang Wei
Published: February 2023

A novel Gram-positive, aerobic, rod-shaped, non-motile, endospore-forming salt-tolerant bacterium strain (80T), was isolated from woodland soil collected near Kanas lake in the Altay region of Xinjiang, PR China. The strain grew at 15−45 °C, pH6.0–9.0 and with 0–14 % (w/v) NaCl. The complete genome size of the novel strain was 4 031 766 bp including a circle chromosome and a circle plasmid. The genomic DNA G+C content was 38.99 mol %. Phylogenetic analysis based on 16S rRNA gene sequence and genome showed that strain 80T has the highest similarity to

Radiobacillus deserti

TKL69T. However, the novel strain showed an average nucleotide identity value of 78.65 % (lower than 95 %) and a digital DNA–DNA hybridization value of 22.30 % with

R. deserti

TKL69T based on the genome sequences. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0, anteiso-C17:0 and C16 : 1 ω7c alcohol. The only respiratory quinone was MK-7. The cell wall peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid, one unidentified aminophospholipid and two unidentified glycolipids were identified as the major polar lipids. The phylogenetic, phenotypic and chemotaxonomic analyses showed that strain 80T represents a novel species of the genus

Radiobacillus

and the name Radiobacillus kanasensis sp. nov. is proposed. The type strain is 80T (=GDMCC 1.2844T=JCM 35077T).
MALAT1Expression is Associated with Aggressive Behavior in Indolent B-Cell Neoplasms
Authors: María Fernández-Garnacho Elena , Nadeu Ferran , Martín Silvia , Mozas Pablo , Rivero Andrea , Delgado Julio , Giné Eva , López-Guillermo Armando , Duran-Ferrer Martí , Salaverria Itziar , López Cristina , Beà Sílvia , Demajo Santiago , Jares Pedro , Puente Xose S , Martín-Subero José Ignacio , Campo Elias , Hernández Lluís
Published: February 2023

MALAT1is a long non-coding RNA with oncogenic roles in cancer but poorly studied in indolent B-cell neoplasms. Here,MALAT1expression was analyzed using RNA-seq, microarrays or qRT-PCR in primary samples from various clinico-biological subtypes of chronic lymphocytic leukemia (CLL, n=266) and follicular lymphoma (FL, n=61). In peripheral blood (PB) CLL samples, highMALAT1expression was associated with a significantly shorter time to treatment, independently from other known prognostic factors, such as IGHV mutational status. Coding genes whose expression levels were associated withMALAT1in CLL were predominantly related to oncogenic pathways stimulated in the lymph node (LN) microenvironment. Further analysis ofMALAT1expression by microarrays in paired CLL samples from PB/LN showed that its levels were maintained between both anatomical compartments, supporting that the clinical value ofMALAT1expression found in PB is mirroring expression differences already present in LN. Similarly, highMALAT1expression in FL predicted for a shorter progression-free survival, and its correlated expressed genes were associated with pathways promoting FL pathogenesis. In summary,MALAT1expression is related to pathophysiology and clinical behavior of indolent B-cell neoplasms. Particularly in CLL its levels could be a surrogate marker of the microenvironment stimulation and may contribute to refine the clinical management of these patients.
BRIEF COMMUNICATION: High level of Anti SARS-Co-V2 RBD Antibody one year post booster vaccine hospital workers in Indonesia; Was second booster needed?
Authors: Muslimah Amila Hanifan , Tiara Marita Restie , Djauhari Hofiya , Dewantara Hafizh , Susandi Evan , Indrati Agnes Rengga , Alisjahbana Bachti , Soeroto Arto Yuwono , Wisaksana Rudi
Published: February 2023

Healthcare workers in Indonesia acquired a complete 2 doses of Sinovac in early 2021 and first booster dose of Moderna in July 2021. In August 2022, the ministry of health prioritized healthcare workers to acquire the second booster dose of Moderna as antibody levels from the year before may have waned. We conducted a sequential serosurvey aimed to determine the level of SARS CoV2 S-RBD antibody reached by the first vaccine, after the first booster, and before the second booster to understand the dynamics of the antibody level. COVID-19 antibody test was conducted using the FastBioRBDtmtest with a maximum limit detection level of 4000 BAU/mL. First serosurvey which was conducted in June 2021, one to six months after Sinovac vaccination, showed a median antibody level of 41.4 BAU/mL (IQR 10 – 629.4 BAU/mL). The second serosurvey was conducted one month (August 2021) after the first Moderna booster vaccine, and showed a median level of 4000 BAU/mL (IQR 3081 – 4000 BAU/mL). While the last serosurvey conducted a year (August 2022) after the booster, showed 4000 BAU/mL (IQR 4000 – 4000 BAU/mL). Only 39 (11.9%) healthcare workers have antibody levels below the maximum level of 4000 BAU./mL We did not see the waning of antibody levels among healthcare workers approximately 1 year after the booster. It increases perhaps due to the natural infection caused by the omicron variant outbreak in early 2022. Based on this fact, we suggest considering if the second booster dose is really necessary. The limited vaccine supply can better be given to the person or other high-risk groups of patients who has a low level of antibody based on serological testing.
Towards automatic home-based sleep apnea estimation using deep learning
Authors: Retamales Gabriela , Gavidia Marino E. , Bausch Ben , Montanari Arthur N. , Husch Andreas , Goncalves Jorge
Published: February 2023

Apnea and hypopnea are common sleep disorders characterized by complete or partial obstructions of the airways, respectively. A sleep study, also known as polysomnography (PSG), is typically used to compute the Apnea–Hypopnea Index (AHI), the number of times a person has apnea or certain types of hypopnea per hour of sleep. AHI is then used to diagnose the severity of the sleep disorder. Early detection and treatment of apnea can significantly reduce morbidity and mortality. However, continuous PSG monitoring is unfeasible as it is costly and uncomfortable for patients. To circumvent these issues, we propose a method, named DRIVEN, to estimate AHI at home from wearable devices and assist physicians in diagnosing the severity of apneas. DRIVEN also detects when apnea, hypopnea, periods of wakefulness occur throughout the night, facilitating easy inspection by physicians. Patients can wear a single sensor or a combination of sensors that can be easily measured at home: abdominal movement, thoracic movement, or pulse oximetry. For example, using only two sensors, DRIVEN correctly classifies 72.4% of all test patients into one of the four AHI classes, with 99.3% either correctly classified or placed one class away from the true one. This is a reasonable trade-off between the model’s performance and patient’s comfort. We use data from three sleep studies from the National Sleep Research Resource (NSRR), the largest public repository, consisting of 14,370 recordings. DRIVEN is based on a combination of deep convolutional neural networks and a light-gradient-boost machine for classification. Since DRIVEN is simple and computationally efficient, it can be implemented for automatic estimation of AHI in unsupervised long-term home monitoring systems, reducing costs to healthcare systems and improving patient care.
Prevalence of Screen Addiction and its association with Screen Use Behavior & Type of Content Consumed in the general population of Mumbai & its environs
Authors: Rao Shirish , Gupta Vidushi , Ambike Amey , Adarkar Shilpa , Mhatre Pauras , Saraf Prashant , Raul Shreeya , Paranjape Raghav , Dedhia Keval , Inamdar Gayatri , Chavan Pavan , Shinde Purva , Kadam Esha
Published: February 2023

Background

Varied prevalence of internet, gaming & smartphone addiction have been estimated across different regions. Though gaming & internet addiction have already been recognized, the emerging trend of binge-watching also demands attention. There was a need to estimate their prevalence using a uniform scale, compare addiction scores and also assess its association with content consumed and screen use behavior.

Objective

To find the prevalence of screen addiction and its association with screen use behaviour & type of content consumed.

Methodology

A cross-sectional study was conducted among 252 participants who were recruited using stratified random sampling and were interviewed using Digital Addiction Scale & a self-designed questionnaire (CVR>0.65).

Results

The prevalence of screen addiction was found to be 13% and found to be associated with age(p<0.01), sex(p<0.01), type of content consumed(p<0.05), device used(p<0.01), self-reported causes(p<0.01), withdrawal(p<0.01) & screen use specific psychological phenomenon(p<0.01). Addiction scores of gamers, social media users & binge watchers were comparable(p>0.05).

Conclusion

The prevalence of screen addiction is substantially high, particularly in the younger population. This study also highlights the strong association of screen use behavior & type of content consumed and apps used with addictive screen use. The similarity in addiction scores and associated factors also support the use of umbrella term ‘Screen Addiction’ to group all kinds of addictive screen usage.
DOC screen completion time reflects executive function, speed of processing and fluency in an observational cohort study
Authors: Southwell Alisia , Sujanthan Sajeevan , Armel Tera , Xing Elaine , Kapoor Arunima , Eileen Liu Xiao Yu , Lanctot Krista L. , Herrmann Nathan , Murray Brian J. , Thorpe Kevin E. , Cayley Megan L. , Sicard Michelle N. , Lien Karen , Sahlas Demetrios J. , Swartz Richard H.
Published: February 2023

Background

The DOC screen was developed to identify Depression, Obstructive sleep apnea, and Cognitive impairment (“DOC” comorbidities) after stroke. Each component has its own score, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure. We assessed the added value of using DOC screen completion time as a predictor of impairment on detailed cognitive assessments.

Methods

Consecutive English-speaking new referrals to the stroke prevention clinic were consented to participate in detailed neuropsychological testing (n=437). DOC screen scores and times were compared to cognitive test scores using multiple linear regression and receiver operating characteristic (ROC) analysis. All linear regression analyses controlled for age, sex, years of education, and functional outcome as assessed by the modified Rankin score.

Results

Average completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for age, sex and cognitive screen score, completion time was a significant independent predictor, of speed of processing (p = .002, 95% CI: -0.016 to -0.004), verbal fluency (p < .001, CI: -0.012 to -0.006) and executive (p = .004, CI: -0.006 to -0.001), but not memory, function. Completion time above 5.5 minutes (332.5 seconds) was associated with a high likelihood of impairment on gold standard executive (likelihood ratios 3.9-5.2) and speed of processing (likelihood ratio = 5.2) tasks.

Conclusions

DOC screen completion time is easy to collect in routine care and is independently associated with speed of processing, language and executive dysfunctions after stroke. People who take more than 5.5 minutes to complete the DOC screen are likely to have deficits in executive functioning and speed of processing. These domains can be challenging to screen for in stroke survivors, and this measure provides a simple, clinically feasible method to screen for these under-appreciated concerns.

Clinical Trials Registration Identifier:NCT02363114

Clinical Trials URL:https://clinicaltrials.gov/ct2/show/NCT02363114
Distinct and shared genetic architectures of Gestational diabetes mellitus and Type 2 Diabetes Mellitus
Authors: Elliott A. , Walters R. K. , Pirinen M. , Kurki M. , Junna N. , Goldstein J. , Reeve M.P. , Siirtola H. , Lemmelä S. , Turley P. ,   FinnGen, Palotie A. , Daly M. , Widén E.
Published: February 2023

Gestational diabetes mellitus (GDM) affects more than 16 million pregnancies annually worldwide and is related to an increased lifetime risk of Type 2 diabetes (T2D). The diseases are hypothesized to share a genetic predisposition, but there are few GWAS studies of GDM and none of them is sufficiently powered to assess whether any variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen Study and identified 13 GDM-associated loci including 8 novel loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into two distinct categories – one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis, and placental expression. These results pave the way for an improved biological understanding of GDM pathophysiology and its role in the development and course of T2D.
Machine learning prediction of early postpartum prediabetes in women with gestational diabetes mellitus
Authors: Parkhi Durga , Periyathambi Nishanthi , Weldeselassie Yonas , Patel Vinod , Sukumar Nithya , Siddharthan Rahul , Narlikar Leelavati , Ponnusamy Saravanan
Published: February 2023

Background

Early onset of type 2 diabetes and cardiovascular disease are common complications for women diagnosed with gestational diabetes. About half of the women with gestational diabetes develop postpartum prediabetes within 10 years of the index pregnancy. These women also have double the risk of developing cardiovascular disease than women without a history of gestational diabetes. Currently, there is no accurate way of knowing which women with gestational diabetes are likely to develop postpartum prediabetes. This study aims to predict the risk of postpartum prediabetes in women diagnosed with gestational diabetes.

Methods

We build a sparse logistic regression-based machine learning model to learn key variables significant for the prediction of postpartum prediabetes, from antenatal data with maternal anthropometric and biochemical variables as well as neonatal characteristics of 607 UK women diagnosed with gestational diabetes. We evaluate the performance of the proposed model in addition to other more advanced machine learning methods using established metrics such as the area under the receiver operating characteristic curve and specificity for pre-determined values of sensitivity. We use K-L divergence and information graphs to evaluate and compare different thresholds of classification for targeted screening options in resource-constrained settings. We also perform a decision curve analysis to study the net standardized benefit of our model compared to the universal screening approach.

Results

Strikingly, our sparse logistic regression approach selects only two variables as relevant but gives an area under the receiver operating characteristic curve of 0.72, outperforming all other methods. It can identify postpartum prediabetes in women with gestational diabetes using the Rule-in test with 92% specificity at an optimal probability threshold of 0.381 and using the Rule-out test with 92% sensitivity at an optimal probability threshold of 0.140.

Conclusion

We propose a simple logistic regression model, which needs only the antenatal fasting glucose at OGTT and HbA1c soon after the diagnosis of GDM, to predict, with remarkable accuracy, the probability of postpartum prediabetes in women with gestational diabetes. We envision this to be a practical solution, which coupled with a targeted follow-up of high-risk women, could yield better cardiometabolic outcomes in women with a history of GDM.
A comprehensive survey on the beliefs, perceptions, and clinical manifestations of pre and post Covid-19 vaccinations among physiotherapy students in the United Arab Emirates
Authors: Almheiri Shaikha , Hazari Animesh , Kumar Praveen , Kumar Sampath , Girish Srilatha
Published: February 2023

Background

The World Health Organization has defined Coronavirus Disease (COVID-19) as an infectious pandemic, caused by a newly discovered SARS-CoV-2 virus. Students relied heavily on the internet, social media, parents, and friends, in addition to medical advice for information on its presentation, complications, prevention, and management. It is evident from the literature that healthcare professionals including students who play an important role in the healthcare system may be lacking important information on COVID-19 vaccinations. Thus, the study aims to identify and compare the pre-post covid-19 vaccination-related essential information among Physical Therapy university students.

Methods

A cross-sectional survey was conducted among physiotherapy university students in the United Arab Emirates using a self-administrated structured questionnaire. The questionnaire comprised three sections covering beliefs, perceptions, and clinical manifestations of the pre and post-COVID-19 vaccination. The survey was shared with more than 300 students through email and social platforms during the time between January 2022 till December 2022.

Results

The majority of the physiotherapy students believed the vaccines to be safe (71.3%) due to multiple reasons while others did not believe in the effectiveness of the vaccine (28.7%). Some students did report unusual symptoms (painful periods, hair loss, forgetfulness) after the vaccine (10%). Similar findings were reported for family members as well (14%). Students had a positive perception of the vaccine and reported willingness to take it even if not mandatory (68%).

Conclusion

Some students did believe in the safety of the vaccine due to multiple reasons while some did not due to fear of long-term side effects and personal choices. The finding of the study could be useful to create confidence as well as awareness among physiotherapy students as they are often invited to aid during medical pandemics such as Covid 19. Also, higher rates of vaccination among healthcare professionals will impart higher acceptance in the medical organization due to safety guidelines. This could also help to counsel other students against fear and apprehension towards the vaccination of such kind in the future.
Changes in SARS-CoV-2 seroprevalence and population immunity in Finland, 2020–2022
Authors: Solastie Anna , Nieminen Tuomo , Ekström Nina , Nohynek Hanna , Lehtonen Lasse , Palmu Arto A. , Melin Merit
Published: February 2023

1.

Studying the prevalence of SARS-CoV-2 specific antibodies (seroprevalence) allows assessing the impact of epidemic containment measures and vaccinations, as well as estimation of the number of infections regardless of viral testing. We assessed antibody-mediated immunity to SARS-CoV-2 induced by infections and vaccinations from April 2020 to December 2022 in Finland by measuring serum IgG to SARS-CoV-2 nucleoprotein (N-IgG) and spike glycoprotein from randomly selected 18-85-year-old subjects (n=9794). N-IgG seroprevalence remained at <7% until the last quartile (Q) of 2021. After the emergence of the omicron variant, N-IgG seroprevalence increased rapidly and was 31% in Q1/2022 and 54% in Q4/2022. Seroprevalence was highest in youngest age groups from Q2/2022 onwards. We estimated that 51% of the Finnish 18-85-year-old population had antibody-mediated hybrid immunity induced by a combination of vaccinations and infections by the end of 2022. In conclusion, major shifts in the COVID-19 pandemic and resulting population immunity could be observed by serological testing.
Evidence of Leaky Protection Following COVID-19 Vaccination and SARS-CoV-2 Infection in an Incarcerated Population
Authors: Lind Margaret L , Dorion Murilo , Houde Amy J , Lansing Mary , Lapidus Sarah , Thomas Russell , Yildirim Inci , Omer Saad B. , Schulz Wade L. , Andrews Jason R. , Hitchings Matt DT , Kennedy Byron S. , Richeson Robert P. , Cummings Derek AT , Ko Albert I
Published: February 2023

Whether SARS-CoV-2 infection and COVID-19 vaccines confer exposure-dependent (“leaky”) protection against infection remains unknown. We examined the effect of prior infection, vaccination, and hybrid immunity on infection risk among residents of Connecticut correctional facilities during periods of predominant Omicron and Delta transmission. Residents with cell, cellblock, and no documented exposure to SARS-CoV-2 infected residents were matched by facility and date. During the Omicron period, prior infection, vaccination, and hybrid immunity reduced the infection risk of residents without a documented exposure (HR: 0.36 [0.25-0.54]; 0.57 [0.42-0.78]; 0.24 [0.15-0.39]; respectively) and with cellblock exposures (0.61 [0.49-0.75]; 0.69 [0.58-0.83]; 0.41 [0.31-0.55]; respectively) but not with cell exposures (0.89 [0.58-1.35]; 0.96 [0.64-1.46]; 0.80 [0.46-1.39]; respectively). Associations were similar during the Delta period and when analyses were restricted to tested residents. Although associations may not have been thoroughly adjusted due to dataset limitations, the findings suggest that prior infection and vaccination may be leaky, highlighting the potential benefits of pairing vaccination with non-pharmaceutical interventions in crowded settings.
A comparative mixed method study of flipped class room and traditional lecture for teaching rational drug prescription among undergraduates in Pharmacology
Authors: Sushama Jitha , Pulikkunnel Scaria Thomas
Published: February 2023

Rational drug prescription is a very important competency an Indian Medical Graduate (IMG) should acquire during his undergraduate training. Irrational prescriptions lead to drug resistance, adverse drug reactions (ADRs) and drug interactions. This was a prospective interventional mixed – method study where students were pseudo-randomised to either Traditional Lecture or Flipped Classroom based on the date of their academic session. For the study purpose, 250 phase 2 MBBS students in Pharmacology were divided into two groups. Allocation into 2 groups was done by lot method one week before the scheduled class so that the online study materials could be sent to the students belonging to the flipped classroom method in the form of case scenarios and videos. A total of 198 students participated in the study with 103 in the TL group and 95 in the FC group. Acquisition of higher order cognitive skills like application and analysis was assessed by measuring an academic score obtained from a series of exercises on rational prescription in a given clinical scenario. The academic score of the TL group (Mean - 5.99, SD-2.34) vs FC (Mean-5.59, SD-1.39) group thus obtained was not statistically significant p > 0.05, Effect size-0.08. The perception of students towards TL and FC assessed with the help of a questionnaire showed a statistically significant difference in favour of FC for the perceptions in the ability to improve academic score, generate peer interaction, facilitate team work and improve teacher-student interaction.
Single-cell transcriptomic atlas of Alzheimer’s disease middle temporal gyrus reveals region, cell type and sex specificity of gene expression with novel genetic risk for MERTK in female
Authors: Zhang Le , He Chuan Hua , Coffey Sarah , Yin Dominic , Hsu I-Uen , Su Chang , Ye Yixuan , Zhang Chi , Spurrier Joshua , Nicholson LaShae , Rothlin Carla V. , Ghosh Sourav , Gopal Pallavi P. , Hafler David A. , Zhao Hongyu , Strittmatter Stephen M.
Published: February 2023

Alzheimer’s disease, the most common age-related neurodegenerative disease, is closely associated with both amyloid-ß plaque and neuroinflammation. Two thirds of Alzheimer’s disease patients are females and they have a higher disease risk. Moreover, women with Alzheimer’s disease have more extensive brain histological changes than men along with more severe cognitive symptoms and neurodegeneration. To identify how sex difference induces structural brain changes, we performed unbiased massively parallel single nucleus RNA sequencing on Alzheimer’s disease and control brains focusing on the middle temporal gyrus, a brain region strongly affected by the disease but not previously studied with these methods. We identified a subpopulation of selectively vulnerable layer 2/3 excitatory neurons that that were RORB-negative and CDH9-expressing. This vulnerability differs from that reported for other brain regions, but there was no detectable difference between male and female patterns in middle temporal gyrus samples. Disease-associated, but sex-independent, reactive astrocyte signatures were also present. In clear contrast, the microglia signatures of diseased brains differed between males and females. Combining single cell transcriptomic data with results from genome-wide association studies (GWAS), we identifiedMERTKgenetic variation as a risk factor for Alzheimer’s disease selectively in females. Taken together, our single cell dataset revealed a unique cellular-level view of sex-specific transcriptional changes in Alzheimer’s disease, illuminating GWAS identification of sex-specific Alzheimer’s risk genes. These data serve as a rich resource for interrogation of the molecular and cellular basis of Alzheimer’s disease.
Estimating the Genetic Contribution to Astigmatism and Myopia in the Mexican population
Authors: Román-López Talía V. , García-Vilchis Brisa , Murillo-Lechuga Vanessa , Chiu-Han Enrique , Xanat López-Camaño , Aldana-Assad Oscar , Diaz-Torres Santiago , Caballero-Sánchez Ulises , Ivett E. Ortega-Mora I. , Ramirez-Gonzalez Diego , Zenteno Diego , Espinosa-Valdés Zaida , Tapia-Atilano Andrea , Pradel-Jiménez Sofía , Rentería Miguel E. , Medina-Rivera Alejandra , Ruiz-Contreras Alejandra E. , Alcauter Sarael
Published: February 2023

Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including student learning and productivity. Current understanding suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twins diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated in Mexican twins, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method. The results showed a concordance rate of 0.74 for MZ twins and 0.50 for DZ twins for astigmatism, and a higher concordance rate in MZ twins, 0.74, compared to DZ twins, 0.54 for myopia. Heritability estimates were 0.66 for astigmatism and 0.62 for myopia, with a cross-trait genetic correlation of rA=0.82 and a phenotypic correlation of rP=0.80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.
Ethical dilemma arises from optimising interventions for epidemics in heterogeneous populations
Authors: Kollepara Pratyush K. , Chisholm Rebecca H. , Kiss István Z. , Miller Joel C.
Published: February 2023

Interventions to mitigate the spread of infectious diseases, while succeeding in their goal, have economic and social costs associated with them. These limit the duration and intensity of the interventions. We study a class of interventions which reduce the reproduction number and find the optimal strength of the intervention which minimises the final epidemic size for an immunity inducing infection. The intervention works by eliminating the overshoot part of an epidemic, and avoids a second-wave of infections. We extend the framework by considering a heterogeneous population and find that the optimal intervention can pose an ethical dilemma for decision and policy makers. This ethical dilemma is shown to be analogous to the trolley problem. We apply this optimisation strategy to real world contact data and case fatality rates from three pandemics to underline the importance of this ethical dilemma in real world scenarios.
Phenome-wide analysis ofAPOL1risk variants reveals associations between one combination of haplotypes and multiple disease phenotypes in addition to chronic kidney disease
Authors: Adamson Walt E. , Noyes Harry , Johnson Paul , Cooper Anneli , Monckton Darren G. , Ogunsola John , Sullivan Michael , Mark Patrick , Parekh Rulan S. , MacLeod Annette
Published: February 2023

Background

Infectious diseases are a major driving force of natural selection. One human gene associated with strong evolutionary selection isAPOL1. TwoAPOL1variants, G1 and G2, emerged in sub-Saharan Africa in the last 10,000 years, possibly due to protection from the fatal African sleeping sickness, analogous toPlasmodium-driven selection of the sickle-cell trait. As homozygosity for the HbS allele causes sickle cell anaemia, homozygosity for theAPOL1G1 and G2 variants has also been associated with chronic kidney disease (CKD) and other kidney-related conditions. What is not known is the extend of non-kidney-related disorders and if there are clusters of diseases associated with individual APOL1 genotypes.

Methods

Using principal component analysis, we identified a cohort of 10,179 UK Biobank participants with recent African ancestry. We conducted a phenome-wide association test between all combinations ofAPOL1G1 and G2 genotypes and conditions identified with International Classification of Disease phenotypes using Firth’s bias-reduced logistic regression and a false discovery rate to correct for multiple testing. We further examined associations with chronic kidney disease indicators: estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine (uACR).

Results

The phenome-wide screen revealed 74 (mostly deleterious) potential associations with hospitalisation for a range of conditions. G1/G2 compound heterozygotes were specifically associated with hospitalisation in 64 (86.5%) of these conditions, with an over-representation of infectious diseases (including COVID-19) and endocrine, nutritional, and metabolic diseases. The analysis also revealed complexities in the relationship betweenAPOL1and CKD that are not evident when the risk variants are grouped together: high uACR was associated specifically with G1 homozygosity; low eGFR with G2 homozygosity and G1/G2 compound heterozygosity; progression to end stage kidney disease was associated with G1/G2 compound heterozygosity.

Conclusions

Among 9,594 participants, stratifying individualAPOL1risk variant genotypes had a differential effect on associations with both kidney and non-kidney phenotypes. The compound heterozygous G1/G2 genotype was distinguished as uniquely deleterious in its association with a range of ICD-10 phenotypes. The epistatic nature of the G1/G2 interaction means that such associations may go undetected in a standard genome-wide association study. These observations have the potential to significantly impact the way that health risks are understood, particularly in populations whereAPOL1G1 and G2 are common such as in sub-Saharan Africa and its diaspora.