bluuebunny/crossref_metadata_2025 huggingface dataset:
Finite Element Analysis to Study Tensile Strength Differences between Free and Attached Ear Lobules
Authors: Vathulya Madhubari , Sarkar Subrato , Verma Vaishali , Singh Indra Vir , Kandwal Pankaj
Published: February 2023

Recurrent ear lobule deformity is a chronic condition with aesthetic implications. The problem is normally addressed by certain improvisations of the traditional lobuloplasty technique. These include introduction of autologous tissue components like cartilage pieces to improve the structural integrity. Certain authors also advocate a different site for repiercing of the ear hole away from the lobuloplasty scar. Our study tries to understand the differences in the tensile strength between free and attached ear lobules, using finite element analysis. Eighteen healthy female volunteers with attached (eight subjects) and free ear lobules (10 subjects) were chosen, and the lobules were scanned using Artec 3D scanner. The model was then converted to free form or attached form (opposite to the form in which it was present originally) by decreasing or increasing the area of contact using geomagic software. Finite element analysis was then performed on both the models, and their yield max and, hence, the maximum load at the yield max at 0.7 strains according to previous studies were estimated and compared. The yield max and the corresponding load were found to be lesser in the free variety than in the attached variety. This experiment helps us to understand that when a structural difference in the ear lobule surgically may bring about a change in the tensile strength of the lobules. However, further clinical trials are required to clinically translate the same.
Successful Use of WALANT in Local and Regional Soft Tissue Flaps: A Case Series
Authors: Connors Katherine M. , Kurtzman Joey S. , Koehler Steven M.
Published: February 2023

Background:

The wide awake local anesthesia no tourniquet (WALANT) technique has been proven to be safe and effective for upper extremity surgery. WALANT does not require extensive medical clearance and allows for intraoperative assessment of range of motion. Additionally, it is frequently associated with lower costs and less postoperative pain when compared with traditional methods of anesthesia. Despite its expanded use for hand procedures, there are sparse data to support the use of WALANT in local and regional soft tissue flaps.

Methods:

A retrospective review was performed. Twenty-one patients who underwent a local or regional soft tissue flap surgery using the WALANT technique from February 2, 2018 to February 25, 2022 were included in our analysis.

Results:

Overall, one Louvre flap, two posterior tibial artery perforator propeller flaps, two reverse radial forearm flaps, two Quaba flaps, six cross finger flaps, one reverse homodigital island flap, three first dorsal metacarpal artery flaps, two thenar flaps, and two Moberg flaps were performed. Patients were followed up for an average of 11.9 ± 8.1 weeks. During this time, no postoperative complications occurred. All patients demonstrated appropriate healing at donor and recipient sites. Full range of motion was regained for all patients.

Conclusions:

WALANT is safe and effective for use in local and regional soft tissue flap surgery. Surgeons should consider this technique for more involved procedures such as flap surgery, as preliminary results demonstrate positive outcomes and potentially superior recovery for patients.
Evaluating sleep in covert encephalopathy with wearable technology: results from the WATCHES study
Authors: Buckholz Adam , Clarke Lindsay , Paik Paul , Jesudian Arun , Schwartz Robert , Krieger Ana , Rosenblatt Russell , Brown Robert S.
Published: February 2023

Background and Aims:

Covert HE (CHE) is a common early stage of HE associated with poor outcomes. Available neuropsychiatric diagnostic testing is underutilized and has significant clinical limitations. Sleep deterioration is consistently associated with CHE and HE; however, objective data is sparse and it has not been studied longitudinally. We longitudinally study and describe an association of sleep metrics with CHE as detected by a commercial wearable technology.

Methods:

We monitored sleep for 6 months using a commercial fitness tracker in 25 participants with cirrhosis, hypothesizing that CHE as diagnosed by psychometric testing would be associated with significant reductions in sleep quality, especially restorative sleep (deep sleep + rapid eye movement). Mixed-effects modeling was performed to evaluate sleep factors associated with CHE and developed and internally validated a score based on these sleep metrics for associated CHE.

Results:

Across 2862 nights with 66.3% study adherence, we found that those with CHE had consistently worse sleep, including an average of 1 hour less of nightly restorative sleep, driven primarily by reductions in rapid eye movement. A model including albumin, bilirubin, rapid eye movement, sleep disturbances, and sleep consistency showed good discrimination (area under the receiver operating curve=0.79) for CHE status with a sensitivity of 76% and specificity of 69%.

Conclusions:

Our large longitudinal study of sleep in cirrhosis suggests that sleep derangements in CHE can be detected using wearable technology. Given the known importance of sleep to overall health and CHE/HE to prognosis in cirrhosis, the ability to associate dynamic sleep metrics with CHE may in the future help with the detection and passive monitoring as factors that precipitate decompensation of cirrhosis become better understood and mobile health data validation and integration improves.
Can remnant cholesterol (triglyceride-rich lipoproteins) reclassify estimated risk of atherosclerotic cardiovascular disease?
Authors: Doi Takahito , Nordestgaard Børge G. , Langsted Anne
Published: February 2023

Purpose of review

To summarize recent studies analyzing reclassification of estimated risk of myocardial infarction (MI) and ischemic heart disease (IHD) by inclusion of remnant cholesterol (= cholesterol content in triglyceride-rich lipoproteins) in primary and secondary prevention settings.

Recent findings

For individuals in a primary prevention setting with remnant cholesterol levels at least 95th percentile (≥1.6 mmol/l, 61 mg/dl), 23% of MI and 21% of IHD events developed later were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Overall improved reclassification of MI was also observed for remnant cholesterol levels as low as at least 50th percentile (≥0.6 mmol/l, 25 mg/dl); however, the addition of remnant cholesterol over the entire concentration range yielded insignificant improvements of NRI for MI but slightly improved reclassification of NRI for IHD. In a secondary prevention setting, addition of remnant cholesterol over the entire concentration range to a conventional risk model improved reclassification.

Elevated remnant cholesterol levels considerably improves reclassification of individuals who later develop MI and IHD, in primary as well as in secondary prevention settings.
Fascia promotes adipose tissue regeneration by improving early macrophage infiltration following fat grafting in mice model
Authors: Bi Xin , Li Bin , Zou Jialiang , Zhao Jing , Chen Yunzi , Wang Xinhui , Lu Feng , Li Ye , Dong Ziqing , Gao Jianhua
Published: February 2023

Background:

Low early macrophage fat graft infiltration (within a week of surgery) hinders tissue regeneration, suggesting that macrophages play a vital role in early angiogenesis and adipogenesis. However, the source of macrophages during this period is unclear.

Method:

C57BL/6 mice were split into fascial removal (FR) and control groups (CG). Mice had a piece of back fascia removed in the FR, which was immediately replaced in the CG, and inguinal fat injected into the transplantation site of both groups. Separately, fascia was harvested from green fluorescent protein-expressing mice and transplanted into C57BL/6 mice for tracing the macrophages infiltration after fat grafting.

Results:

The number of capillaries in the FR group was lower than that in the CG at days 3 (p<0.01) and 7 (p<0.05). Moreover, the number of small adipocytes in the FR group was lower than in the CG on days 3, 7 and 14(all p<0.05), and the relative expression of several adipogenic proteins was significantly lower in the FR group than in the CG on days 14 and 30. The timeline of macrophage infiltration was consistent with angiogenesis and adipogenesis. The number of macrophages in the FR group was significantly lower than in the CG at days 3 and 7(p<0.05), and there were more fascia-derived macrophages than circulation-derived macrophages infiltrated into fat grafts within 7 days. Finally, the graft retention was lower in the FR group than the CG at day 90 (p<0.05).

Conclusion:

In the early stage following fat grafting, fascial macrophages infiltration initiates tissue regeneration, thereby improving graft retention by promoting angiogenesis and adipogenesis.
Effects of Delayed Graft Function on Transplant Outcomes: A Meta-analysis
Authors: Li Miah T. , Ramakrishnan Adarsh , Yu Miko , Daniel Emily , Sandra Vanessa , Sanichar Navin , King Kristen L. , Stevens Jacob S. , Husain S. Ali , Mohan Sumit
Published: February 2023

Delayed graft function (DGF) is a frequent complication of kidney transplantation, but its impact on long- and short-term transplant outcomes is unclear. We conducted a systematic literature search for studies published from 2007 to 2020 investigating the association between DGF and posttransplant outcomes. Forest plots stratified between center studies and registry studies were created with pooled odds ratios. Posttransplant outcomes including graft failure, acute rejection, patient mortality, and kidney function were analyzed. Of the 3422 articles reviewed, 38 papers were included in this meta-analysis. In single-center studies, patients who experienced DGF had increased graft failure (odds ratio [OR] 3.38; 95% confidence interval [CI], 1.85-6.17; P < 0.01), acute allograft rejection (OR 1.84; 95% CI, 1.30-2.61; P < 0.01), and mortality (OR 2.32; 95% CI, 1.53-3.50; P < 0.01) at 1-y posttransplant. Registry studies showed increased graft failure (OR 3.66; 95% CI, 3.04-4.40; P < 0.01) and acute rejection (OR 3.24; 95% CI, 1.88-5.59; P < 0.01) but not mortality (OR 2.27; 95% CI, 0.97-5.34; P = 0.06) at 1-y posttransplant. DGF was associated with increased odds of graft failure, acute rejection, and mortality. These results in this meta-analysis could help inform the selection process, treatment, and monitoring of transplanted kidneys at high risk of DGF.
SARS-CoV-2 Spike Protein Receptor Binding-ACE2 Interaction Increases Carbohydrate Sulfotransferases and Reduces N-Acetylgalactosamine-4-Sulfatase through Phospho-p38-MAPK and RB-E2F1
Authors: Bhattacharyya Sumit , Tobacman Joanne K.
Published: January 2023

Immunohistochemistry of post-mortem lung tissue from patients with SARS-CoV2 infection showed marked decline in intensity and distribution of N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB), increase of total chondroitin sulfate by immunohistochemistry, and increase of vascular-associated carbohydrate sulfotransferase (CHST)15 [1]. The mechanisms leading to these observations were not explained by signaling pathways known to be activated by exposure to coronaviruses. This report addresses the underlying reactions leading to these observations in a cell-based model, using normal, human, primary small airway epithelial cells, treated with the SARS-CoV-2 spike protein receptor binding domain protein.
Child and Adolescent Psychiatrists’ Use, Attitudes, and Understanding of Genetic Tests in Clinical Practice
Authors: Soda Takahiro , Merner Amanda R. , Small Brent J. , Torgerson Laura N. , Muñoz Katrina , Austin Jehannine , Storch Eric A. , Pereira Stacey , Lázaro-Muñoz Gabriel
Published: January 2023

Objective

To report current practices and attitudes of child and adolescent psychiatrists (CAP) regarding diagnostic genetic and pharmacogenetic (PGx) testing.

Methods

Survey of 958 US-based practicing CAP.

Results

54.9% of respondents indicated that they had ordered/referred for a genetic test in the past 12 months. 87% of respondents agreed that it is their role to discuss genetic information regarding psychiatric conditions with their patients; however, 45% rated their knowledge of genetic testing practice guidelines as poor/very poor. The most ordered test was PGx (32.2%), followed by chromosomal microarray (23.0%). 73.4% reported that PGx is at least slightly useful in child and adolescent psychiatry. Most (62.8%) were asked by a patient/family to order PGx in the past 12 months and 41.7% reported they would order PGx in response to a family request. Those who ordered a PGx test were more likely to have been asked by a patient/family and to work in private practice. 13.8% of respondents agreed/strongly agreed that a PGx test can predict the effectiveness of specific antidepressants. Some respondents also indicated they would make clinical changes based on PGx information even if a medication was currently effective and there were no side effects.

Conclusions

Genetic testing has become routine clinical care in child and adolescent psychiatry. Despite this, many providers rate their associated knowledge as poor/very poor. Patient requests were associated with ordering practices and providers misinterpretation of PGx may be leading to unnecessary changes in clinical management. There is need for further education and support for clinicians.
Associations of Healthy Lifestyle and Socioeconomic Status with Cognitive Function in U.S. Older Adults
Authors: Wang Xin , Bakulski Kelly M. , Paulson Henry L. , Albin Roger L. , Park Sung Kyun
Published: January 2023

We investigated the complex relations of socioeconomic status (SES) and healthy lifestyles with cognitive functions among older adults in 1,313 participants, aged 60 years and older, from the National Health and Nutrition Examination Survey 2011-2014. Cognitive function was measured using an average of the standardized z-scores of the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning and delayed recall tests, the Animal Fluency Test, and the Digit Symbol Substitution Test. Latent class analysis of family income, education, occupation, health insurance, and food security was used to define composite SES (low, medium, high). A healthy lifestyle score was calculated based on smoking, alcohol consumption, physical activity, and the Healthy-Eating-Index-2015. In survey-weighted multivariable linear regressions, participants with 3 or 4 healthy behaviors had 0.07 (95% CI: 0.005, 0.14) standard deviation higher composite cognitive z-score, relative to those with one or no healthy behavior. Participants with high SES had 0.37 (95% CI: 0.29, 0.46) standard deviation higher composite cognitive z-score than those with low SES. No statistically significant interaction was observed between healthy lifestyle score and SES. Our findings suggested that higher healthy lifestyle scores and higher SES were associated with better cognitive function among older adults in the United States.
Left atrial substrate characterization based on bipolar voltage electrograms acquired with multipolar, focal and mini-electrode catheters– the CHAZE-Substrate study
Authors: Knecht Sven , Schlageter Vincent , Badertscher Patrick , Krisai Philipp , Jousset Florian , Spies Florian , Küffer Thomas , Madaffari Antonio , Schaer Beat , Osswald Stefan , Sticherling Christian , Kühne Michael
Published: January 2023

Background

Bipolar voltage (BV) electrograms for left atrial (LA) substrate characterization depend on catheter design and electrode configuration. The aim of the study was to investigate the relationship between the BV amplitude (BVA) using four different catheters and to identify their specific LA cutoffs for scar and healthy tissue.

Methods

Consecutive high-resolution electroanatomic mapping was performed using a multipolar Orion catheter (Orion-map), a duo-decapolar variable circular mapping catheter (Lasso-Map) and an irrigated focal ablation catheter with minielectrodes (Mifi-map). Virtual remapping using the Mifi-map was performed with a 4.5 mm tip-size electrode configuration (Nav-map). BVAs were compared in voxels of 3×3×3 mm3. The equivalent BVA cutoff for every catheter was calculated for established reference cutoff values of 0.1 mV, 0.2 mV, 0.5 mV, 1.0 mV, and 1.5 mV.

Results

We analyzed 25 patients (72% men, age 68±15 years). For scar tissue, a 0.5 mV cutoff using the Nav corresponds to a lower cutoff of 0.35 mV for the Orion and of 0.48 mV for the Lasso. Accordingly, a 0.2 mV cutoff corresponds to a cutoff of 0.09 mV for the Orion and of 0.14 mV for the Lasso. For a healthy tissue cutoff at 1.5 mV, a larger BVA cutoff for the small electrodes of the Orion and the Lasso was determined of 1.68 mV and 2.21 mV, respectively.

Conclusions

When measuring LA BVA in scar and healthy tissue, relevant differences were seen between focal, multielectrode and mini-electrode catheters. Adapted cutoffs for scar and healthy tissue are required.
The Selah trial: A preference-based partially randomized waitlist control study of three stress management interventions
Authors: Proeschold-Bell Rae Jean , Eagle David E. , Tice Logan C. , Platt Alyssa , Yao Jia , Larkins Jessie S. , Kim Eunsoo Timothy , Rash Joshua A.
Published: January 2023

Objective

Chronic stress can undermine psychological and physiological health. We sought to evaluate three stress management interventions among clergy, accounting for intervention preferences.

Methods

United Methodist clergy in North Carolina enrolled in a partially randomized, preference-based waitlist control trial. The interventions were: mindfulness-based stress reduction (MBSR), Daily Examen prayer practice, and Stress Proofing (stress inoculation plus breathing skills). The intervention period spanned 12 weeks with a 12-week follow-up. Daily text message data were collected to assess practice across the 24 weeks. Co-primary outcomes were symptoms of stress using the Calgary Symptoms of Stress Inventory and 48-hour ambulatory heart rate variability (HRV) at 12-weeks post-intervention compared to waitlist control. Survey data were collected at 0, 12 and 24 weeks, with HRV collected at 0 and 12 weeks.

Results

255 participants (mean age=54 years old; 91% white; 48% female) were randomized and initiated an intervention (n=184) or waitlist control (n=71). Compared to waitlist control, lower stress symptoms were found for MBSR participants [Mean Difference (MD)=-0.30, 95% CI:-0.41,-0.20;p<.001] and Stress Proofing (MD=-0.27, 95% CI:-0.40,-0.14;p<.001) at 12 weeks, and Daily Examen participants not until 24 weeks (MD=-0.24, 95% CI:-0.41,-0.08). Only MBSR participants demonstrated improvement in HRV at 12 weeks (MD=+3.32 millisecond; 95% CI:0.21,6.44;p=.036).

Conclusions

MBSR demonstrated robust improvement in self-reported and objective physical correlates of stress whereas Stress Proofing and Daily Examen resulted in improvements in self-reported correlates of stress only. These brief practices were sustainable and beneficial for an occupational sample during the COVID pandemic.

Registration

ClinicalTrials.govidentifier:NCT04625777(https://clinicaltrials.gov/ct2/show/NCT04625777)
A transcriptomic approach to understand patient susceptibility to pneumonia after abdominal surgery
Authors: Torrance Hew D , Zhang Ping , Longbottom E Rebecca , Mi Yuxin , Whalley Justin P , Allcock Alice , Kwok Andrew J , Cano-Gamez Eddie , Geoghegan Cyndi G , Burnham Katie L , Antcliffe David B , Davenport Emma E , Pearse Rupert M , O’Dwyer Michael J , Hinds Charles J , Knight Julian C , Gordon Anthony C
Published: January 2023

Rationale

Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality.

Objectives

To describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia.

Methods and Measurements

From a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.

Main Results

Compared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptiveimmune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.

Conclusions

Major-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.
Whole exome sequencing and replication for breast cancer among Hispanic/Latino women identifiesFANCMas a susceptibility gene for estrogen-receptor-negative breast cancer
Authors: Nierenberg Jovia L. , Adamson Aaron W. , Hu Donglei , Huntsman Scott , Patrick Carmina , Li Min , Steele Linda , Tong Barry , Shieh Yiwey , Fejerman Laura , Gruber Stephen B. , Haiman Christopher A. , John Esther M. , Kushi Lawrence H. , Torres-Mejía Gabriela , Ricker Charité , Weitzel Jeffrey N. , Ziv Elad , Neuhausen Susan L.
Published: January 2023

Introduction

Breast cancer (BC) is one of the most common cancers globally. Genetic testing can facilitate screening and risk-reducing recommendations, and inform use of targeted treatments. However, genes included in testing panels are from studies of European-ancestry participants. We sequenced Hispanic/Latina (H/L) women to identify BC susceptibility genes.

Methods

We conducted a pooled BC case-control analysis in H/L women from the San Francisco Bay area, Los Angeles County, and Mexico (4,178 cases and 4,344 controls). Whole exome sequencing was conducted on 1,043 cases and 1,188 controls and a targeted 857-gene panel on the remaining samples. Using ancestry-adjusted SKAT-O analyses, we tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. We calculated odds ratios (OR) for BC using ancestry-adjusted logistic regression models. We also tested the association of single variants with BC risk.

Results

We saw a strong association of LoF variants inFANCMwith ER-negative BC (p=4.1×10−7, OR [CI]: 6.7 [2.9-15.6]) and a nominal association with overall BC risk. Among known susceptibility genes,BRCA1(p=2.3×10−10, OR [CI]: 24.9 [6.1-102.5]),BRCA2(p=8.4×10−10, OR [CI]: 7.0 [3.5-14.0]), andPALB2(p=1.8×10−8, OR [CI]: 6.5 [3.2-13.1]) were strongly associated with BC. There were nominally significant associations withCHEK2, RAD51D, andTP53.

Conclusion

In H/L women, LoF variants inFANCMwere strongly associated with ER-negative breast cancer risk. It previously was proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested in clinical practice. Our results demonstrate thatFANCMshould be added to BC gene panels.
Determinants of Under-nutrition among Children Aged 6 up to 59 Months in Akaki Kaliti Sub City, Addis Ababa: Unmatched Case-Control Study
Authors: Kebede Abeje , Getaneh Dagmawit , Asfaw Derbachew , Birhanu Addis
Published: January 2023

Background

Malnutrition remains a major health problem and globally it is responsible for one-third of all infant and child mortality. Despite progress has been made in improving child nutrition in Ethiopia in the last decades, it remains a problem of public health importance. Though, there were numerous studies undertaken previously, no studies were previously tried to verify the determinants of malnutrition among children age 6 to 59 months in the study area. Hence, there is a necessity to carry out a study to come up with the determinant factors of malnutrition in the Akaki Kaliti sub-city, Addis Ababa.

Objective of the Study

To identify determinants of undernutrition among children age 6 to 59 months in Akaki Kaliti Sub-city, Addis Ababa, 2021.

Methods and Materials

Facility-based unmatched case control study was conducted in public health facilities of Akaki Kaliti Sub-city, Addis Ababa from April 26 to May 31, 2021. Consecutive sampling technique was employed. Primary data was collected using interviewer-administered structured questionnaire and analyzed using SPSS for windows version 21. Variables with P-value <0.25 in the bivariate analysis were identified and fitted in multivariable logistic regression model to identify independent predictors of child undernutrition. The magnitude of association was measured by AOR with 95% confidence interval. A P-value less than 0.05 were used to declare the observed association is statistically significant.

Result

A total of 83 children (cases) and 159 children (controls) with their mothers/care givers were participated in the study. Having upper respiratory tract infection in the past two weeks [AOR = 1.89; 95%CI (1.2 – 3.57)], lack of water supply to the household [AOR = 2.93; 95%CI (1.3 – 6.57)], and use of public toilet facility [AOR = 2.35; 95%CI (1.21 – 4.57)] were factors statistically significant with the outcome variables.

Conclusion and Recommendation

having upper respiratory tract infection in the past two weeks, not having water supply to the household, and using public toilet facilities had contributed to the risk of undernutrition. Strengthening screening of all children for undernutrition and improving water and sanitation services to the household are recommended.
Using the Index of Concentration at the Extremes to Evaluate Associations of Income and Black-White Racial Segregation with HIV Outcomes Among Adults Aged ≥18 Years — United States and Puerto Rico, 2019
Authors: Gant Zanetta , Dailey André , Hu Xiaohong , Song Wei , Beer Linda , Johnson Lyons Shacara , Denson Damian J. , Satcher Johnson Anna
Published: January 2023

Objective(s)

To examine associations between Index of Concentration at the Extremes (ICE) measures for economic and racial segregation and HIV outcomes in the United States (U.S.) and Puerto Rico.

Methods

County-level HIV testing data from CDC’s National HIV Prevention Program Monitoring and Evaluation and census tract-level HIV diagnoses, linkage to HIV medical care, and viral suppression data from the National HIV Surveillance System were used. Three ICE measures of spatial polarization were obtained from the U.S. Census Bureau’s American Community Survey: ICEincome (income segregation), ICErace (Black-White racial segregation), and ICEincome+race (Black-White racialized economic segregation). Rate ratios (RRs) for HIV diagnoses and prevalence ratios (PRs) for HIV testing, linkage to care within 1 month of diagnosis, and viral suppression within 6 months of diagnosis were estimated with 95% confidence intervals (CIs) to examine changes across ICE quintiles using the most privileged communities (Quintile 5, Q5) as the reference group.

Results

PRs and RRs showed a higher likelihood of testing and adverse HIV outcomes among persons residing in Q1 (least privileged) communities compared with Q5 (most privileged) across ICE measures. For HIV testing percentages and diagnosis rates, PRs and RRs were consistently greatest for ICErace. For linkage to care and viral suppression, PRs were consistently lower for ICEincome+race.

Conclusions

Income, racial, and economic segregation—as measured by ICE—might contribute to poor HIV outcomes and disparities by unfairly concentrating certain groups (i.e., Black persons) in highly segregated and deprived communities that experience a lack of access to quality, affordable health care. Expanded efforts are needed to address the social/economic barriers that might impede access to HIV care among Black persons. Increased partnerships between government agencies and the private sector are needed to change policies that promote and sustain racial and income segregation.
Difficulty with Mobility among the Aged in Ghana: Evidence from Wave 2 of the World Health Organization’s study on Global Ageing and Adult Health
Authors: Boakye Kingsley , Aidoo Antoinette Ama , Aliyu Mohammed , Boateng Daniel , Nakua Emmanuel Kweku
Published: January 2023

Background

The recent decline in mortality, increase in life expectancy and technological and scientific advancements have led to an increasingly ageing population. About 727 million people globally were aged 65 or more in 2020, and 1 in 6 people will be age 65 years or above by 2050. About 7% of Ghana’s population was over 60 years in 2010, and projected to be 12% by 2050. However, the aged are confronted with degenerative conditions that translate into difficulty with mobility. The study was conducted to investigate the difficulty with mobility among the aged in Ghana.

Methods

The study utilised a cross-sectional dataset of the 2014/2015 (wave 2) Study on Global Ageing and Adult Health and included 1,848 participants aged ≥50 years. The survey command was applied to adjust for sampling biases and the design of the study. At 5% alpha level, a chi-square test of independence was conducted to determine the association between dependent and independent variables. At 95% confidence interval and 5% alpha level, three-level multilevel logistic regression models were performed. The fixed-effects were presented in odds ratio and the random effects were presented using the Intra-Class Correlation. All analysis were performed using STATA statistical software version 16.0.

Results

Out of the 1,848 participants, 62.3% had difficulty with mobility. Additionally, age (80 and above) [AOR=4.70, 95%CI=2.34 – 9.43], difficulty performing household activities [AOR=6.96, 95%CI=5.03 – 9.64], experiencing bodily pains [AOR=3.21, 95%CI=1.81 – 5.60] and bodily discomfort [AOR=3.39, 95%CI=1.91 – 5.99] and difficulty with vision [AOR=1.70, 95%CI=1.18 – 2.43] had higher odds of difficulty with mobility. However, engaging in vigorous activities [AOR=0.44, 95%CI=0.32 – 0.63] and having good health [AOR=0.41, 95%CI=0.19 – 0.88] were protective of difficulty with mobility.

Conclusion

The study concludes that the aged in Ghana had higher prevalence (62.3%) of difficulty with mobility which is associated with age (80 and above), difficulty performing household activities, bodily pains and discomfort, and difficulty with vision. This suggests the need to provide support and assistive devices for the aged and provide geriatric care including recreational fields and care homes to address the health and physical needs of the aged in Ghana.
Ultrasound and biochemical predictors of pregnancy outcome at diagnosis of early-onset fetal growth restriction
Authors: Spencer Rebecca , Maksym Kasia , Hecher Kurt , Maršál Karel , Figueras Francesc , Ambler Gareth , Whitwell Harry , Nené Nuno Rocha , Sebire Neil J. , Hansson Stefan R. , Diemert Anke , Brodszki Jana , Gratacós Eduard , Ginsberg Yuval , Weissbach Tal , Peebles Donald M , Zachary Ian , Marlow Neil , Huertas-Ceballos Angela , David Anna L.
Published: January 2023

Background

Severe early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, preventing accurate patient counselling. We investigated the use of maternal serum protein and ultrasound measures at diagnosis to predict fetal or neonatal death and three secondary outcomes: fetal death or delivery ≤28+0 weeks; development of abnormal umbilical artery Doppler velocimetry; slow fetal growth.

Methods

Women with singleton pregnancies (n=142, estimated fetal weights [EFWs] <3rdcentile, <600g 20+0-26+6 weeks of gestation, no known chromosomal, genetic or major structural abnormalities), were recruited from four European centres. Maternal serum from the discovery set (n=63) was analysed for seven proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease and five proteins identified through pooled liquid chromatography tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n=60), with final models calculated from combined data.

Results

The most discriminative model for fetal or neonatal death included EFW z-score (Hadlock 3 formula/Marsal chart), gestational age and umbilical artery Doppler category (AUC 0.91, 95%CI 0.86-0.97) but was less well calibrated than the model containing only EFW z-score (Hadlock3/Marsal). The most discriminative model for fetal death or delivery ≤28+0 weeks included maternal serum placental growth factor (PlGF) concentration and umbilical artery Doppler category (AUC 0.89, 95%CI 0.83-0.94).

Conclusion

Ultrasound measurements and maternal serum PlGF concentration at diagnosis of severe early-onset FGR predict pregnancy outcomes of importance to patients and clinicians.

Trial registration

ClinicalTrials.govNCT02097667

Funding

European Union, Rosetrees Trust, Mitchell Charitable Trust.
Antidepressant and antipsychotic drug prescribing and complications of diabetes: a systematic review of observational studies
Authors: Greene Charlotte R L , Ward-Penny Hanna , Ioannou Marianna F , Wild Sarah H , Wu Honghan , Smith Daniel J , Jackson Caroline A
Published: January 2023

Aims

Psychotropic medication may be associated with adverse effects, particularly in people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and diabetes outcomes.

Methods

We systematically searched PubMed, EMBASE, and PsycINFO to 15thAugust 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis.

Results

We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality and highly heterogeneous in terms of study population, exposure definition and outcome analysed. Antidepressant prescribing may be associated with increased risk of macrovascular outcomes, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported on microvascular complications and cardiometabolic factors other than glycaemic control and just one study reported on antipsychotics and diabetes complications.

Conclusions

There has been little study of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes. Further, more methodologically robust, research is needed to inform and enhance antidepressant and antipsychotic drug prescribing and monitoring practices in people with diabetes.
Can medication mentions in CRIS be used for researching medication use in older people with dementia? Comparing the natural language processing app for medicines to GP prescribing
Authors: Davis Katrina A.S. , Broadbent Matthew , Bishara Delia , Mueller Christoph , Stewart Robert
Published: January 2023

Background

The efficacy of long-term preventative medication in people who have dementia and other comorbidities is unknown. Electronic health record-based observational studies may play a role in evaluating medicines, and SLaM-CRIS is one such resource. Medication in SLaM-CRIS is extracted from structured and unstructured fields using a natural language processing app. We aimed to compare the results from the medication app with GP prescribing, using an innovative data link with primary care (Lambeth DataNet, LDN) that covers around one-quarter of the SLaM-CRIS population.

Methods

A cohort was created of people with both LDN record and SLaM-CRIS record who had received a diagnosis of dementia in either record, in which ascertainment of medication could be compared. Ten classes of medication commonly taken long-term for preventative purposes were studied (aspirin, statins, ACE inhibitors, anticoagulants, beta-blockers, bisphosphonates, calcium with vitamin D, non-aspirin antiplatelets, proton pump inhibitors and antidepressants), plus medications taken for dementia itself. Mentions of these medication classes in SLaM-CRIS from around the time of dementia diagnosis were extracted using a natural language processing application. Prescription issue for the same medications was extracted from LDN in the year of dementia diagnosis and compared with that from SLaM-CRIS on a cohort and individual level.

Results

Our sample included 4410 with documentation of dementia in either SLaM-CRIS or LDN. Estimation of the prevalence of the use of each medication in CRIS was compared to LDN, and was within +/-3 per 100, except for calcium with vitamin D supplement, where SLaM-CRIS prevalence was 13 people per 100 lower than LDN (8.6% vs 21.2%). Medication ascertainment of all groups except calcium with vitamin D supplement showed good agreement (kappa above 0.7), and very good agreement for antidepressants and dementia drugs (kappa above 0.8). Sensitivity was highest for dementia drugs and antidepressants (above 90%), 85% for statins and 75% for aspirin. Restricting to those with a memory clinic referral did not change the levels of agreement.

Discussion

Routinely collected data cannot provide a gold-standard measure of what medications are truly taken by patients with dementia, but several sources can provide a proxy measure. This analysis supports the use of the natural language processing application for medication in SLaM-CRIS to extract medication mentions of relevance to people with dementia, as compared to prescribing from the GP at around the same time. However, some medications show low sensitivity, possibly due to low recording or inconsistency in the text used to record, and enhancement will be needed before studying these medications.
Examining the impact of the COVID-19 pandemic on cervical cancer screening practices among clinicians practicing in Federally Qualified Health Centers: A mixed methods study
Authors: Fuzzell Lindsay , Lake Paige , Brownstein Naomi C. , Fontenot Holly B. , Whitmer Ashley , Michel Alexandra , McIntyre McKenzie , Rossi Sarah L. , Kajtezovich Sidika , Vadaparampil Susan T. , Perkins Rebecca
Published: January 2023

Background

The COVID-19 pandemic led to reductions in cervical cancer screening and colposcopy. Therefore, in this mixed method study we explored perceived pandemic-related practice changes to cervical cancer screenings in federally qualified health centers.

Methods

Between October 2021 and June 2022, a national sample of 148 clinicians completed surveys; a subset (n=13) clinicians completed qualitative interviews. Most (86%) reported reduced cervical cancer screening early in the pandemic, and 28% reported continued reduction in services at the time of survey completion (October 2021-July 2022). Nearly half (45%) reported staff shortages impacting their ability to screen or track patients.

Results

Compared to clinicians in OBGYN/Women’s health, those in family medicine and other specialties were less likely to report maintaining or increasing screening compared to pre-pandemic. Advanced practice providers (compared to MDs/DOs,) and Hispanic/Latinx/other clinicians (compared to white non-Hispanic) were more likely to report maintaining or increasing screening vs. pre-pandemic. Most (91%) felt that screening using HPV self-sampling would be helpful to address screening backlogs. Qualitative interviews highlighted the impacts of staff shortages and strategies for improvement.

Conclusions

Identifying barriers to screening and instituting solutions in federally qualified health centers is critical to preventing cervical cancers among patients at highest risk.

Funding

This study was funded by the American Cancer Society, who had no role in the study’s design, conduct, or reporting.
Analysis of large-language model versus human performance for genetics questions
Authors: Duong Dat , Solomon Benjamin D.
Published: January 2023

Large-language models like ChatGPT have recently received a great deal of attention. To assess ChatGPT in the field of genetics, we compared its performance to human respondents in answering genetics questions (involving 13,636 responses) that had been posted on social media platforms starting in 2021. Overall, ChatGPT did not perform significantly differently than human respondents, but did significantly better on memorization-type questions versus critical thinking questions, frequently provided different answers when asked questions multiple times, and provided plausible explanations for both correct and incorrect answers.
Vitamin interdependencies predicted by metagenomics-informed network analyses validated in microbial community microcosms
Authors: Hessler Tomas , Huddy Robert J. , Sachdeva Rohan , Lei Shufei , Harrison Susan T.L. , Diamond Spencer , Banfield Jillian F.
Published: January 2023

Microbial communities are fundamental components of most ecosystems but little is known about the interactions that structure them. Metagenomic data have revolutionized our understanding of complex consortia, yet predicted interactions are rarely explored experimentally. We developed an organism abundance correlation network to investigate factors that control community organization in soil-derived laboratory microbial consortia grown under dozens of conditions. The network was overlaid with metagenomic information about functional capacities to generate testable hypotheses. We developed a metric to predict the importance of each node within its local network environments relative to correlated vitamin auxotrophs and predicted that aVariovoraxspecies is a hub because it is a highly important source of thiamine. Quantification of thiamine during the growth ofVariovoraxin minimal media conditions showed extraordinarily high levels of production of thiamine, up to 100 mg/L. This over-production of thiamine explains why the auxotrophs correlated withVariovoraxare reliant on this organism for thiamine, despite the presence of other predicted thiamine producers in the community. A few of these thiamine auxotrophs are predicted to produce pantothenate that we show thatVariovoraxrequires to grow, implying that a subset of vitamin-dependent interactions are mutualistic. We found thatCryptococcusproduces the B-vitamin pantothenate, and co-cultures led to a 90-130-fold fitness increase for bothCryptococcusandVariovorax. This study demonstrates the predictive power of metagenome-informed, microbial consortia-based network analyses for identifying microbial interactions that underpin the structure and functioning of microbial communities.
Early HIV-1 Gag Assembly on Lipid Membrane with vRNA
Authors: Zhou Anne X.-Z. , Hammond John A. , Sheng Kai , Millar David P. , Williamson James R.
Published: January 2023

Mass photometry (MP) was used to investigate the assembly of myristoylated full-length HIV-1 Gag (myr-Gag) and vRNA 5’ UTR fragment in a supported lipid bilayer (SLB) model system. The MP trajectories demonstrated that Gag trimerization on the membrane is a key step of early Gag assembly in the presence of vRNA. Growth of myr-Gag oligomers requires vRNA, occuring by addition of 1 or 2 monomers at a time from solution. These data support a model where formation of the Gag hexamers characteristic of the immature capsid lattice occurs by a gradual edge expansion, following a trimeric nucleation event. These dynamic single molecule data involving protein, RNA, and lipid components together, provide novel and fundamental insights into the initiation of virus capsid assembly.
Three-dimensional genomic mapping of human pancreatic tissue reveals striking multifocality and genetic heterogeneity in precancerous lesions
Authors: Braxton Alicia M , Kiemen Ashley L , Grahn Mia P , Forjaz André , Babu Jaanvi Mahesh , Zheng Lily , Jiang Liping , Cheng Haixia , Song Qianqian , Reichel Rebecca , Graham Sarah , Damanakis Alexander I , Fischer Catherine G , Mou Stephanie , Metz Cameron , Granger Julie , Liu Xiao-Ding , Bachmann Niklas , Almagro-Pérez Cristina , Jiang Ann Chenyu , Yoo Jeonghyun , Kim Bridgette , Du Scott , Foster Eli , Hsu Jocelyn Y , Rivera Paula Andreu , Chu Linda C , Liu Fengze , Niknafs Noushin , Fishman Elliot K , Yuille Alan , Roberts Nicholas J , Thompson Elizabeth D , Scharpf Robert B , Cornish Toby C , Jiao Yuchen , Karchin Rachel , Hruban Ralph H , Wu Pei-Hsun , Wirtz Denis , Wood Laura D
Published: January 2023

Pancreatic intraepithelial neoplasia (PanIN) is a precursor to pancreatic cancer and represents a critical opportunity for cancer interception. However, the number, size, shape, and connectivity of PanINs in human pancreatic tissue samples are largely unknown. In this study, we quantitatively assessed human PanINs using CODA, a novel machine-learning pipeline for 3D image analysis that generates quantifiable models of large pieces of human pancreas with single-cell resolution. Using a cohort of 38 large slabs of grossly normal human pancreas from surgical resection specimens, we identified striking multifocality of PanINs, with a mean burden of 13 spatially separate PanINs per cm3of sampled tissue. Extrapolating this burden to the entire pancreas suggested a median of approximately 1000 PanINs in an entire pancreas. In order to better understand the clonal relationships within and between PanINs, we developed a pipeline for CODA-guided multi-region genomic analysis of PanINs, including targeted and whole exome sequencing. Multi-region assessment of 37 PanINs from eight additional human pancreatic tissue slabs revealed that almost all PanINs contained hotspot mutations in the oncogeneKRAS, but no gene other thanKRASwas altered in more than 20% of the analyzed PanINs. PanINs contained a mean of 13 somatic mutations per region when analyzed by whole exome sequencing. The majority of analyzed PanINs originated from independent clonal events, with distinct somatic mutation profiles between PanINs in the same tissue slab. A subset of the analyzed PanINs contained multipleKRASmutations, suggesting a polyclonal origin even in PanINs that are contiguous by rigorous 3D assessment. This study leverages a novel 3D genomic mapping approach to describe, for the first time, the spatial and genetic multifocality of human PanINs, providing important insights into the initiation and progression of pancreatic neoplasia.