bluuebunny/crossref_metadata_2025 huggingface dataset:
Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease
Authors: Sun Ying , Wang Bin , Yu Yuefeng , Wang Yuying , Tan Xiao , Zhang Jihui , Qi Lu , Lu Yingli , Wang Ningjian
Published: March 2024

Background:

Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).

Methods:

In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.

Results:

Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5–4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00–1.16) in men and 1.23 (1.16–1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age (P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0–1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01–5.13] in men; 4.24 [3.33–5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17–1.58]) could be decomposed into 24.7% (95% CI: 15.0%–34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%–72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%–18.6%) for their additive interaction in women.

Conclusions:

Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.
The Utility of a Novel Bidirectional Lateral Intercostal Artery Perforator Flap for Reconstructing Partial Mastectomy Defects
Authors: Schwartz Jean-Claude D.
Published: March 2024

Smaller breasts require volume replacement to allow for breast conservation for large tumor to breast size ratios. The lateral intercostal artery perforator (LICAP) flap is one of the most commonly used approaches to replace volume as it readily fills lateral breast defects where most cancers typically arise. The LICAP flap was initially described with the bulk of its tissue volume oriented posteriorly, lateral to the breast footprint. Recently, the “reverse LICAP” flap was described, which uses the same perforators but recruits tissue instead from below the inframammary fold. Here, we combine these two approaches, preserving the same perforators, but harvesting tissue from both below the inframammary fold and lateral to the breast footprint, to create a single, larger, bidirectional LICAP flap. This modified flap replaces more volume than previously described for uni-directional approaches allowing us to potentially avoid mastectomy or more extensive flap reconstructions. Here, we describe 10 consecutive patients where the bidirectional LICAP flap was used to facilitate oncoplastic breast conservation.
Improving Time to Angioembolization for Trauma Care: Novel Smartphone Application
Authors: Miles Gayla , Quinlan Ann
Published: March 2024

BACKGROUND:

Timely angiographic embolization of abdominopelvic injuries is a hallmark of a high-functioning trauma center. Yet, the process depends on the timely mobilization of interventional radiology staff. Smartphone technology to notify and mobilize staff may be a viable option.

OBJECTIVE:

To describe the incorporation of a smartphone application into our trauma workflow process previously developed for stroke care.

METHODS:

In 2022, our Level I trauma center implemented a smartphone application with three simultaneously occurring functions: (a) high-definition image viewing on the phone; (b) text messaging thread for all parties; and (c) a single-call activation system for staff mobilization. The application was initially developed to notify interventional radiologists of large-vessel occlusions in victims of stroke and, at our request, was modified to fit our trauma workflow process. The smartphone application company developed a new program, installed the application on trauma service smartphones, and provided educational in-services over a 1-month period. The application was then integrated into our trauma workflow process.

RESULTS:

The trauma surgeon and the interventional radiologist can now simultaneously view high-definition images on their smartphones. Text messages are accessible to all team members. The staff is notified and mobilized with the singlecall smartphone application, preventing the placing and returning of phone calls.

CONCLUSION:

Smartphone technology enhances timely interventional radiology staff response for hemorrhagic patients requiring emergent angioembolization.
Trauma Patient-Centered Discharge Plan Form: A Pilot Study
Authors: Stricker Lisa G. , Running Alice , Lucas Amanda H. , McKenzie Barry A.
Published: March 2024

BACKGROUND:

Comprehensive and multidisciplinary discharge planning can improve trauma patient throughput, decrease length of hospitalization, increase family and patient support, and expedite hospital discharge.

OBJECTIVE:

This study aimed to assess the feasibility and acceptability of implementing a patient-centered discharge plan form for adult trauma patients.

METHODS:

A single-center pilot study was conducted with adult trauma patients on a neurosurgical medical-surgical floor at a Level II trauma center in the Western United States from January to February 2023. The study had three phases: observation, pilot intervention, and follow-up. The key pilot intervention was the development of a standardized patient-centered discharge plan form, pilot tested by a trauma advanced practice provider and an inpatient discharge nurse. The primary outcome was the frequency of discharge orders being written before noon on the day of discharge. Qualitative and quantitative outcomes are reported.

RESULTS:

The discharge form was used for eight patients during the pilot intervention phase; an advanced practice provider and an inpatient discharge nurse each completed the forms for four patients. Five of eight observed patients had discharge orders before noon; the incidence of orders before noon was slightly higher when the form was completed by the discharge nurse (three of four patients) than by the advanced practice provider (two of four patients).

CONCLUSIONS:

The pilot study found that the patient-centered discharge plan form was feasible and acceptable to help improve the discharge process for trauma patients. Additional work to further refine the form's content and administration is warranted.
Transcutaneous osseointegration for amputees
Authors: Evans Andrew R. , Tetsworth Kevin , Quinnan Stephen , Wixted John J.
Published: March 2024

Transcutaneous osseointegration for amputees (TOFA) is an evolving technology that has the potential to revolutionize the interface between the amputee and their prosthesis, showing potential at many levels of amputation. While no amputation is without its challenges, TOFA requires a highly specialized prosthesis and a multidisciplinary team that includes specialized surgeons, physical therapists, wound care teams, and social workers who guide the amputee through surgery, postoperative rehabilitation, and the chronic wound care that goes into maintaining the prosthesis. The infrastructure required to facilitate care pathways that lead to reliable, successful outcomes are unique in each health care setting, including those in advanced health care systems such as the United States and Australia. This article details the emerging evidence supporting the use of this prosthetic interface design and many of the challenges that providers face when establishing programs to offer this type of care in the United States.
Medicaid Insurance Predicts Increased Postoperative Care Encounters Among Patients on Long-Term Opioid Therapy
Authors: Sharif Limi , Zubieta Caroline S. , Arora Akul , Gunaseelan Vidhya , Waljee Jennifer , Bicket Mark C. , Englesbe Michael , Brummett Chad M.
Published: March 2024

Objective:

This study examined the association between insurance type and postoperative unplanned care encounters among patients on long-term opioid therapy prior to surgery.

Summary Background Data:

Preoperative long-term opioid therapy is associated with unique risks and poorer outcomes following surgery. To date, the extent to which insurance coverage influences postoperative outcomes in this population remains unclear.

Methods:

Among individuals receiving a supply of greater than 120 total days or at least 10 opioid prescriptions in the year prior to surgery, we examined patients with Medicaid or private insurance who underwent abdominopelvic surgery from 2017 to 2021 across 70 hospitals in the state of Michigan. The primary outcome was unplanned care encounters, defined as an emergency department visit or unplanned readmission within 30 days of discharge from surgery. Multivariable logistic regression was used to assess the likelihood of acute care events with insurance type as the primary covariate of interest.

Results:

Among 1212 patients on long-term opioid therapy prior to surgery, 45.6% (n = 553) had Medicaid insurance. Overall, one in eight (n=151) patients met criteria for a postoperative unplanned care encounter within 30 days. The probability of an unplanned encounter was 4.5 percentage points higher among patients with Medicaid insurance compared to private insurance (95% CI: 0.5%, 8.4%).

Conclusions:

Among patients on preoperative long-term opioid therapy, unplanned care encounters were higher among patients with Medicaid when compared to private insurance. While this is likely multifactorial, differences by insurance status may point to disparities in underlying social determinants of health and suggest the need for postoperative care pathways that address these gaps.
Association Of Opioid Prescribing And Consumption With Patient-Reported Experiences And Satisfaction Following Emergency Surgery In Michigan
Authors: Rosenthal Lindsay , Gunaseelan Vidhya , Waljee Jennifer , Bicket Mark , Englesbe Michael , Howard Ryan
Published: March 2024

Objective:

To investigate the relationships between opioid prescribing, consumption, and patient reported outcomes (PROs) in emergency surgery patients.

Summary Background Data:

Overprescribing of opioids for pain management after surgery has become a public health concern and major contributor to opioid misuse and dependency. Current guidelines do not address opioid prescribing following emergency surgical procedures, highlighting the importance of understanding the relationship between opioid prescribing and consumption in this setting.

Methods:

Retrospective analysis of the quantity of opioids prescribed and patient-reported outcomes (PROs) in a population-based setting. The sample included adults 18 years and older undergoing emergency surgery across 69 hospitals in Michigan. Patients were included if they received a discharge opioid prescription and had valid data for opioid consumption and PROs. Surgical procedures took place between January 1, 2018 and December 31, 2020.

Results:

During the study period, a total of 3,742 patients underwent an emergency operation. The mean number of opioid pills prescribed was 9.6 and the mean number of opioid pills consumed was 4.6. In a two-model with logit in the first part and a linear regression in the second, prescription size was significantly associated with both the probability of consumption (aOR 1.02, 95% CI 1.01-1.04) and the amount of consumption conditional on any consumption (coefficient 0.70 95% CI 0.54-0.86).

Conclusions and Relevance:

Patients only consumed half of the opioids they were prescribed after undergoing emergency surgery. Additionally, patients who were given larger prescriptions consumed more opioids, but did not experience less pain, higher satisfaction, better quality of life, or less regret to undergo surgery. Overall, this suggests that opioids may be excessively prescribed to patients undergoing emergency surgical procedures, and that larger prescriptions do not improve the patient experience after surgery.
The Association of Preoperative Opioid Use with Post-Discharge Outcomes
Authors: Frangakis Stephan G. , Kavalakatt Bethany , Gunaseelan Vidhya , Lai Yenling , Waljee Jennifer , Englesbe Michael , Brummett Chad M. , Bicket Mark C.
Published: March 2024

Objective:

To examine the association of prescription opioid fills over the year prior to surgery with postoperative outcomes.

Background:

Nearly one third of patients report opioid use in the year preceding surgery, yet an understanding of how opioid exposure influences patient-reported outcomes after surgery remains incomplete. Therefore, this study was designed to test the hypothesis that preoperative opioid exposure may impede recovery in the postoperative period.

Methods:

This retrospective cohort study used a statewide clinical registry from 70 hospitals linked to opioid fulfillment data from the state’s prescription drug monitoring program to categorize patients’ preoperative opioid exposure as none (naïve), minimal, intermittent, or chronic. Outcomes were patient-reported pain intensity (primary), as well as 30-day clinical and patient-reported outcomes (secondary).

Results:

Compared to opioid-naïve patients, opioid exposure was associated with higher reported pain scores at 30 days after surgery. Predicted probabilities was higher among the opioid exposed versus naive group for reporting moderate pain (43.5% [95% CI 42.6 – 44.4%] vs 39.3% [95% CI 38.5 – 40.1%]) and severe pain (13.% [95% CI 12.5 – 14.0%] vs 10.0% [95% CI 9.5 – 10.5%]), and increasing probability was associated increased opioid exposure for both outcomes. Clinical outcomes (incidence of ED visits, readmissions, and reoperation within 30-days) and patient-reported outcomes (reported satisfaction, regret, and quality of life) were also worse with increasing preoperative opioid exposure for most outcomes.

Conclusions:

This study is the first to examine the effect of presurgical opioid exposure on both clinical and non-clinical outcomes in a broad cohort of patients, and shows that exposure is associated with worse postsurgical outcomes. A key question to be addressed is whether and to what extent opioid tapering before surgery mitigates these risks after surgery.
Association of Neighborhood-Level Socioeconomic Status With Prolapse Management Decision
Authors: Downing Perrin , Dong Shirley M. , Ardizzone Melissa A. , Lynch Courtney D. , Hickman Lisa C.
Published: March 2024

Importance

This study identifies how neighborhood-level socioeconomic status (SES) may affect patients' treatment decisions for pelvic organ prolapse (POP).

Objective

This study aimed to evaluate the association of neighborhood-level SES with the decision of surgical versus conservative POP management.

Study Design

This was a retrospective cohort study of patients newly diagnosed with POP at a tertiary medical center between 2015 and 2021. Patients lost to follow-up or poor surgical candidates were excluded. Patient characteristics, demographics, and treatment selection were abstracted from the electronic health record. Conservative management was defined as expectant, pessary, and/or pelvic floor physical therapy. Five-digit zip codes were linked to the Area Deprivation Index and used as a surrogate for neighborhood-level SES. Area Deprivation Indices were dichotomized at or below the sample median (less disadvantaged area) and above the sample median (more disadvantaged area). Logistic regression models estimated the odds of choosing surgical versus conservative management as a function of the Area Deprivation Index.

Results

A total of 459 patients met the eligibility criteria (non-Hispanic White, 88.2%). The median age was 63 years (interquartile range, 52–70 years), and the majority had stage 2 POP (65.7%). Of all patients, 59.3% had Medicare/Medicaid, 39.9% were privately insured, and 0.9% were uninsured. Furthermore, 74.7% selected surgical management, and 25.3% chose conservative management. Increasing age and higher Pelvic Organ Prolapse Quantification System stage were significantly associated with selecting surgery (P= 0.01). Women residing in a more disadvantaged area had a 67% increased odds of choosing surgical over conservative management (adjusted odds ratio, 1.67; 95% confidence interval, 1.06–2.64) after adjusting for age, race/ethnicity, body mass index, and Pelvic Organ Prolapse Quantification System stage.

Conclusions

Residing in a more disadvantaged zip code was associated with 67% increased odds of choosing surgical versus conservative POP management.
Acute emergence of the intestinal pathobiome after postinjury pneumonia
Authors: Munley Jennifer A. , Kelly Lauren S. , Park Gwoncheol , Drury Stacey K. , Gillies Gwendolyn S. , Coldwell Preston S. , Kannan Kolenkode B. , Bible Letitia E. , Efron Philip A. , Nagpal Ravinder , Mohr Alicia M.
Published: March 2024

BACKGROUND

Previous preclinical studies have demonstrated sex-specific alterations in the gut microbiome following traumatic injury or sepsis alone; however, the impact of host sex on dysbiosis in the setting of postinjury sepsis acutely is unknown. We hypothesized that multicompartmental injury with subsequent pneumonia would result in host sex-specific dysbiosis.

METHODS

Male and proestrus female Sprague-Dawley rats (n = 8/group) were subjected to either multicompartmental trauma (PT) (lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofracture), PT plus 2-hour daily restraint stress (PT/RS), PT with postinjury day 1Pseudomonas aeruginosapneumonia (PT-PNA), PT/RS with pneumonia (PT/RS-PNA), or naive controls. Fecal microbiome was measured on days 0 and 2 using high-throughput 16S rRNA sequencing and Quantitative Insights Into Microbial Ecology 2 bioinformatics analyses. Microbial α-diversity was assessed using Chao1 (number of different unique species) and Shannon (species richness and evenness) indices. β-diversity was assessed using principal coordinate analysis. Significance was defined asp< 0.05.

RESULTS

All groups had drastic declines in the Chao1 (α-diversity) index compared with naive controls (p< 0.05). Groups PT-PNA and PT/RS-PNA resulted in different β-diversity arrays compared with uninfected counterparts (PT, PT/RS) (p= 0.001). Postinjury sepsis cohorts showed a loss of commensal bacteria along with emergence of pathogenic bacteria, with blooms ofProteusin PT-PNA andEscherichia-Shigellagroup in PT/RS-PNA compared with other cohorts. At day 2, PT-PNA resulted in β-diversity, which was unique between males and females (p= 0.004). Microbiome composition in PT-PNA males was dominated byAnaerostipesandParasuterella, whereas females had increasedBarnesiellaandOscillibacter. The PT/RS males had an abundance ofGastranaerophilalesandMuribaculaceae.

CONCLUSION

Multicompartmental trauma complicated by sepsis significantly diminishes diversity and alters microbial composition toward a severely dysbiotic state early after injury, which varies between males and females. These findings highlight the role of sex in postinjury sepsis and the pathobiome, which may influence outcomes after severe trauma and sepsis.
Neuronal antibodies in nonparaneoplastic autoimmune cerebellar ataxias
Authors: Saiz Albert , Graus Francesc
Published: March 2024

Purpose of review

To describe relevant advances in nonparaneoplastic autoimmune cerebellar ataxias (ACA) with neuronal antibodies.

Recent findings

Apart from metabotropic glutamate receptor 1(mGluR1) antibodies, in recent years, the number of neuronal antibodies against surface antigens in ACA has increased with the description of glutamate kainate receptor subunit 2 (GluK2) antibodies in young patients with cerebellitis. Around 20% of patients with contactin-associated protein-like 2 (CASPR2) encephalitis also present prominent cerebellar ataxia. However, isolate cerebellar ataxia is unusual (<4%). Outcome in patients with neuronal antibodies against surface antigens remains suboptimal despite the cerebellar ataxia probably is antibody-mediated.

Concerning neuronal antibodies against intracellular antigens, up to 25% of patients with glutamic acid decarboxylase (GAD) antibodies present transient episodes of vertigo or diplopia that antedate the development of the ACA. There is in-vitro evidence that septin-5 is partially exposed to the membrane and the antibodies may interfere with septin-5 function. The clinical significance of the remaining antibodies against intracellular antigens remains unclear.

The number of antibodies against surface antigens is increasing in ACA, but the response to the immunotherapy remains suboptimal. More studies are needed to clarify the role of most of the antibodies against intracellular antigens described in these patients.
Differences in the region of the Mycoplasma gallisepticum sequences pMGA or vlhA among isolated field strains of laying hens with mycoplasma
Authors: Maya-Rodríguez Linda , Gómez-Verduzco Gabriela , Trigo-Tavera Francisco J. , Moreno-Fierros Leticia , Miranda-Morales Rosa Elena
Published: March 2024

Mycoplasmosis, attributed to Mycoplasma gallisepticum, poses a significant challenge to poultry farming, leading to substantial economic losses and persistent infections within flocks. This bacterium harbors various surface proteins that are crucial for the adhesion, transporter activity, and evasion of the host immune response, facilitating its pathogenicity. One such key surface lipoprotein, referred to as pMGA or vlhA hemagglutinin, plays a pivotal role in adhesion processes. In this study, the clonal regions pMGA1.2 and pMGA1.3, as reported by Markham (M83178.1), were investigated to elucidate differences or similarities in the whole DNA sequences of Myc. gallisepticum field strains. The aim was to analyze sequence diversity within this region. Six internal primers were designed to amplify the target sequence, and isolates were obtained from both eggs and chickens sourced from laying hen flocks. Identification revealed 17 strains of Myc. gallisepticum and four strains of Myc. synoviae, which were confirmed through the mgc2 and 16S rRNA genes, respectively. Positive and negative controls were established using the MGS6 and MSWUV1853 strains. Amplification results indicated a higher frequency of amplification proximal to the C-terminal region, with segments 4 (33.3%) and 6 (27.8%) being the most prevalent. Notably, none of the field strains exhibited the same amplification pattern as MGS6, and none of the strains characterized as Myc. synoviae amplified any primer set.
Upon translation, the amino acid sequences from segments 4 and 6 were found to be compatible with conserved sequences within the Myco_haema protein domains of the genus Mycoplasma, specifically corresponding to Q7NAP3_MYCGA VlhA.3.04. The observed homology suggests a potential genetic transfer, while the variability identified in the pMGA or vlhA gene region of the field strains may have significant implications for protection against Myc. gallisepticum infection in chickens.
Associations of HIV and prevalent type 2 diabetes mellitus in the context of obesity in South Africa
Authors: Magodoro IM , Castle AC , Tshuma N , Goedecke JH , Sewpaul R , Manasa J , Manne-Goehler J , Ntusi NAB , Nyirenda MJ , Siedner MJ
Published: March 2024

It is unclear how rising obesity among people with HIV (PWH) in sub-Saharan Africa (SSA) impacts their risk of type 2 diabetes mellitus (diabetes). Using a South African national cross-sectional sample of adult PWH and their peers without HIV (PWOH), we examined the associations between HIV and prevalent diabetes across the spectrum of body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WtHR). Analyses were sex stratified, and adjusted for age, sociodemographic and behavioral factors. The prevalence of diabetes among males was similar between PWH and PWOH, overall and at all levels of adiposity. In contrast, overall diabetes prevalence was higher among female PWOH than female PWH. However, there were differences according to adiposity such that, compared to female PWOH, relative diabetes prevalence in female PWH was reduced with obesity but accentuated with leanness. These differences in the relationship between adiposity and diabetes by HIV serostatus call for better mechanistic understanding of sex-specific adipose tissue biology in HIV in South Africa, and possibly in other HIV endemic settings in SSA.
Time to death and its determinants among neonates admitted to the Neonatal Intensive Care Unit (NICU) of Woldia Comprehensive Specialized Hospital, Amhara region, northeast Ethiopia: A five-year retrospective study
Authors: Fentaw Nuhamin , Demis Asmamaw
Published: March 2024

Background

Despite an effort to reduce neonatal mortality, Ethiopia is still the leading among the countries with the highest neonatal death. While there have been studies conducted on the overall neonatal mortality rate, there is limited research specifically focusing on the time to death of neonates admitted to the Neonatal Intensive Care Unit (NICU).

Objectives

To assess the survival time of neonatal death (time to death) and its determinants for neonates admitted to the NICU of Woldia Comprehensive Specialized Hospital (WCSH).

Methods

A retrospective cohort study was conducted among 604 neonates admitted to the NICU of Woldia comprehensive specialized hospital from January 2018 to December 2022. The data were entered using Epi-Data version 4.6 and analysis was made using STATA version 14 software. To estimate failure probability, the Kaplan-Meier curve and life table estimate were calculated. The log-rank test was used to examine differences in death rates among different categories. The Cox proportional hazards model was employed to identify determinant variables. In the multivariate Cox analysis, variables with a hazard ratio p-value < 0.05 were considered statistically significant at a 95% confidence interval.

Results

The findings of the study indicate that a total of 604 neonates were included and observed for a cumulative period of 3416 neonate-days. The median time to death among the neonates was 14 days. Out of the reviewed cases, 117 (19.37%) neonates died during the study period. Have no ANC checkup (AHR: 1.68; 95% CI: 1.12-2.52), having bad obstetrics history (AHR: 1.99, 95% CI: 1.28-3.10), having sepsis (AHR: 1.87, 95% CI: 1.23-2.86) and having asphyxia (AHR: 1.64, 95% CI: 1.05-2.58) were increased the hazard of neonatal death.

Conclusion

The overall neonatal mortality incidence was high. ANC checkup, bad obstetrics history, and specific diagnoses, were found to significantly influence the hazard of neonatal mortality. Increase awareness and education programs for the community regarding the importance of ANC visits. Implement protocols for early identification and management of respiratory distress, sepsis and prenatal asphyxia is critical.
Pandemic ST131Escherichia colipresenting the UPEC/EAEC and ExPEC/EAEC hybrid pathotypes recovered from extraintestinal infections in a clinical setting of the Brazilian Amazon region
Authors: Bighi Nathália M. S. , Fonseca Érica L. , Freitas Fernanda S. , Morgado Sérgio M. , Vicente Ana Carolina P.
Published: March 2024

Escherichia coliis part of the commensal microbiota of human’s and animal’s gut. However, they may become pathogenic due to the acquisition of virulence factors that provide the ability to cause intestinal or extraintestinal infections, which makesE. colithe main cause of diarrheagenic diseases and urinary tract infections (UTIs) worldwide, respectively. Some strains, known as hybrids, may harbour a mix of virulence determinants of both diarrheagenic (DEC) and extraintestinalE. coli(ExPEC) pathotypes. Reports of hybridE. coliin Brazil are rare, and the lineages associated with such pathotypes were poorly explored. This study aimed to characterizeE. colistrains recovered from extraintestinal infections in a clinical setting of the Brazilian Amazon Region by means of lineage determination, antibiotic resistance profile, and investigation of DEC and ExPEC virulence markers. Fifteen ExPEC strains were recovered from distinct extraintestinal sites from inpatients of the General Hospital of Roraima (GHR), placed in the Brazilian Amazon region. Antibiotic susceptibility test revealed that all strains were multidrug-resistant and most of them, including those recovered from urine, were resistant to fluoroquinolones, the main therapeutic option for treating UTIs, probably due to the presence of Ser83Leu and Asp87Asn substitutions in GyrA. The MLST analysis revealed the polyclonal nature of these ExPEC strains since 11 STs were determined, including local and pandemic lineages, such as ST69 and ST131. Among the 15 isolates, 12 were classified as hybrids, due to the presence of theaggRvirulence marker of the EnteroaggregativeE. coli(EAEC) pathotype together with at least one ExPEC (iutA, KPSMTII, sfaDE, papC, afaBC, iucD) or UropathogenicE. coli(UPEC) (vat,fuyA,chuAandyfcV)virulence determinants. These UPEC/EAEC (n=10) and ExPEC/EAEC (n=2) hybrid strains were found among distinct lineages, including new STs, and phylogroups (ST131/B2; ST1196/AxB1; ST9403/A; ST12394/A; NEW1-CC14/B2; NEW2-CC155/B1; NEW3-CC155/B1; NEW4-CC131/B2) and, for the first time, a hybrid phenotype was found in the pandemic ST131 lineage in Brazil. Therefore, this study provides new information on the epidemiological scenario of hybridE. colistrains, contributing to a better understanding of the occurrence and pathogenic potential of these organisms.
Primary health care improvement in Benin: Cocreating an evidence-informed policy framework to guide the practices of primary care physicians
Authors: Bello Kéfilath , Criel Bart , Dossou Jean-Paul , Zannou Djimon Marcel , Lepeleire Jan De
Published: March 2024

Introduction

In Benin, policies for guiding the practices of primary care physicians (PCPs) are sparse and incomplete. This leads to sub-optimal use of these relatively rare human resources and reduces their potential contribution to people’s health and well-being. In this study, a policy framework guiding PCPs’ practice in Benin is developed in cooperation with key stakeholders.

Methods

The cocreation was a long-term process spread over several years, culminating in a two-day workshop in Cotonou (Benin’s capital city) in October 2022. The core principles of a successful cocreation process were respected: a clear definition of goals, the participation of all relevant stakeholders, including community members, and evidence-informed discussions.

Results

The resulting policy framework includes four overarching dimensions: first, the objectives assigned to PCPs in Benin; second, their roles and related activities; third, their professional identity; and fourth, the governance arrangements guiding their practices. The policy framework provided concrete recommendations for these dimensions based on the Benin context and international evidence.

Conclusion

The cocreation process was instrumental in developing an evidence-informed and consensual policy framework guiding PCPs’ practices in Benin. The framework may be relevant for other West African countries but must be customised to each country’s context.
Advanced and more advanced revascularization in STEMI patients: which is better?
Authors: Li Yahui , Zhao Chunxia , Yue Xindi , Zhou Ling , Wang DaoWen , Wang Feng
Published: March 2024

Objective

To compare the long-term prognosis of patients who experienced acute ST-segment elevation myocardial infarction and underwent either late percutaneous coronary intervention (PCI) within a period of 2 days to less than 1 week or more advanced PCI within 1 week to less than 1 month.

Methods

We enrolled 198 patients from Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, between June 2019 and August 2022. These patients had experienced acute ST-segment elevation myocardial infarction and underwent either late PCI or more advanced PCI. Long-term follow-up was conducted through outpatient clinic visits or telephone interviews. The study endpoints included all-cause death, nonfatal myocardial infarction, and New York Heart Association class IV heart failure. We utilized the Kaplan-Meier method to illustrate the cumulative incidence of endpoint events in both patient groups. Statistical significance in survival differences was assessed using the log-rank test. Additionally, the Cox proportional risk model was employed to analyze whether the timing of late revascularization procedures had an impact on the long-term prognosis of the patients.

Results

Among the 198 patients included in the study, 108 underwent late PCI, while 90 underwent more advanced PCI. The majority were male (73.74%), with an average age of 62 ± 13 years. The follow-up period averaged 20 (15, 28) months, and all patients successfully completed the follow-up process. Analysis based on the Kaplan-Meier method revealed that the incidence of all-cause death [11.1% vs. 5.6%, P=0.165], nonfatal myocardial infarction [7.4% vs. 7.8%, P=0.922], New York Heart Association class IV heart failure [2.8% vs. 3.3%, P>0.999], and the composite endpoint [18.5% vs. 14.4%, P=0.444] were not statistically significant between the late PCI and more advanced PCI groups. After adjusting for factors like left ventricular ejection fraction, renin-angiotensin system inhibitors, β-blockers, and statins, the results still indicated no statistically significant differences between the two groups in terms of rates for all-cause death, recurrent myocardial infarction, New York Heart Association class IV heart failure, and composite endpoints (P=0.05).

Conclusion

This study’s 20 (15, 28) months follow-up suggests that patients experiencing acute ST-segment elevation myocardial infarction have a comparable prognosis regardless of whether they underwent late or more advanced PCI.
Evolutionary double-bind treatment using radiotherapy and NK cell-based immunotherapy in prostate cancer
Authors: Luddy Kimberly A , West Jeffrey , Robertson-Tessi Mark , Desai Bina , Bursell Taylor M. , Barrett Sarah , O’Sullivan Jacintha , Marignol Laure , Gatenby Robert A , Brown Joel S , Anderson Alexander RA , O’Farrelly Cliona
Published: March 2024

Evolution-informed therapies exploit ecological and evolutionary consequences of drug resistance to inhibit the expansion of treatment-resistant populations and prolong time to progression. One strategy, termed an evolutionary double-bind, uses an initial therapy to elicit a specific adaptive response by the cancer cells, which is then selectively targeted by a follow-on therapy. Here we examine the combination of radiation therapy and immunotherapy as a quantifiable double-bind strategy. Radiotherapy (RT) induces lethal double-strand DNA breaks, but cancer cells can adapt by upregulating DNA damage response pathways. While this evolutionary strategy increases resistance to DNA damaging agents, it also results in enhanced expression of natural killer (NK) cell ligands potentially increasing vulnerability to an immune response.

Using a radiation-resistant human prostate carcinoma cell line (22Rv1), we demonstrate that RT-resistant cells upregulate NK cell ligands, including major histocompatibility complex class I chain-related protein A/B (MICA/B), and poliovirus receptors (PVR1, PVRL2) with a 2-fold increase in sensitivity to NK cell mediated killing.

We investigated this potential evolutionary double bind throughin vitrostudies and evolution-based mathematical models. Radiotherapy alone slowed overall growth but strongly selected for RT-resistant cells. NK cell therapy alone suppressed the RT-resistant population but with a surviving population of radiation-sensitive cells. These dynamics were framed mathematically, and model simulation predicted optimal tumour control would be achieved through initial RT rapidly followed by NK-based immunotherapy. Subsequent experiments confirmed the model prediction. We conclude that radiotherapy and NK cell-based immunotherapy produces an evolutionary double bind that can be exploited in heterogenous tumours to limit RT resistance.
Improving protein function prediction by learning and integrating representations of protein sequences and function labels
Authors: Boadu Frimpong , Cheng Jianlin
Published: March 2024

Motivation

As fewer than 1% of proteins have protein function information determined experimentally, computationally predicting the function of proteins is critical for obtaining functional information for most proteins and has been a major challenge in protein bioinformatics. Despite the significant progress made in protein function prediction by the community in the last decade, the general accuracy of protein function prediction is still not high, particularly for rare function terms associated with few proteins in the protein function annotation database such as the UniProt.

Results

We introduce TransFew, a new transformer model, to learn the representations of both protein sequences and function labels (Gene Ontology (GO) terms) to predict the function of proteins. TransFew leverages a large pre-trained protein language model (ESM2-t48) to learn function-relevant representations of proteins from raw protein sequences and uses a biological natural language model (BioBert) and a graph convolutional neural network-based autoencoder to generate semantic representations of GO terms from their textual definition and hierarchical relationships, which are combined together to predict protein function via the cross-attention. Integrating the protein sequence and label representations not only enhances overall function prediction accuracy over the existing methods, but substantially improves the accuracy of predicting rare function terms with limited annotations by facilitating annotation transfer between GO terms.

Availability

https://github.com/BioinfoMachineLearning/TransFew

Contact

chengji@missouri.edu

Supplementary information

Supplementary data are available .
Cohort profile: the Viral load Cohort North-East Lesotho (VICONEL) from 2016 to 2022 – cohort description, test volumes, predictors of viraemia, and the road ahead
Authors: Brown Jennifer A. , Motaboli Lipontso , Lerotholi Malebanye , Kohler Maurus , Hänggi Kathrin , Mokete Moliehi , Chakela Makobefo G. , Kao Mpho , Kopo Mathebe , Mokebe Moleboheng , Nsakala Bienvenu L. , Lukau Blaise , Ayakaka Irene , Amstutz Alain , Ehmer Jochen , Klimkait Thomas , Glass Tracy R. , Muhairwe Josephine , Chammartin Frédérique , Tschumi Nadine , Labhardt Niklaus D.
Published: March 2024

Purpose

The prospective Viral load Cohort North-East Lesotho (VICONEL) aims to support clinical management and generate scientific evidence to inform HIV care. Specifically, VICONEL allows for monitoring of HIV treatment outcomes and health system performance, encompasses a biobank for further research with routinely collected blood plasma samples of consenting participants, and provides a valuable framework for nested observational and interventional studies.

Participants

VICONEL captures routine viral load test results alongside associated demographic and treatment information among people in care for HIV in Lesotho, southern Africa. As of December 2022, it encompasses all viral load testing from 23 healthcare facilities in two districts of Lesotho.

Findings to date

From January 2016 to December 2022, 114’838 viral load test results were available for 27,472 participants. At the time of the last viral load test, median age was 42 years (interquartile range [IQR]: 33-53); 17,324 (63%) were adult women, 9,273 (34%) adult men, and 870 (3%) children <15 years (age/sex missing for 5); and median time taking antiretroviral therapy (ART) was 6.0 years (IQR 3.0-9.2). Overall, the proportion of cohort participants with viral suppression to <1,000 copies/mL has continually exceeded 90% and has been above 95% since 2020; however, this proportion has consistently been lower among children. Sex, age category / ART regimen core agent (combined variable), time since ART initiation, and district were independently associated with viraemia.

Future plans

VICONEL offers potential for i) further digitalisation and automation of results sharing at the client, facility, and district/national level, ii) integration of additional clinical and diagnostic data, including HIV comorbidities, and iii) embedding randomised trials.

Strengths and limitations

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VICONEL covers all HIV viral load testing from 23 clinics in two districts in Lesotho and is thus highly representative.

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Data capture occurs at the time point of viral load testing; thus, treatment or clinical data are not updated between viral load tests, and reasons for exiting the cohort are not followed up.

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Participant data beyond viral load results are limited to key demographic, clinical, and treatment information.

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The cohort and associated biobank have proven to be a valuable platform for nested observational and interventional research, including randomised trials.

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Core functions can be maintained at low cost, constituting a model for near-real-time monitoring of treatment outcomes with limited resources.
Intra- and interindividual variability in fasted gastric content volume
Authors: Roelofs Julia J.M. , Camps Guido , Leenders Louise M. , Marciani Luca , Spiller Robin C. , van Eijnatten Elise J.M. , Alyami Jaber , Deng Ruoxuan , Freitas Daniela , Grimm Michael , Karhunen Leila J. , Krishnasamy Shanthi , Le Feunteun Steven , Lobo Dileep N. , Mackie Alan R. , Mayar Morwarid , Weitschies Werner , Smeets Paul A.M.
Published: March 2024

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Background

Gastric fluid plays a key role in food digestion and drug dissolution, therefore, the amount of gastric fluid present in a fasted state may influence subsequent digestion and drug delivery. We aimed to describe intra- and interindividual variation in fasted gastric content volume (FGCV) and to determine the association with age, sex, and body size characteristics.

Methods

Data from 24 MRI studies measuring FGCV in healthy, mostly young individuals after an overnight fast were pooled. Analysis included 366 participants with a total of 870 measurements. Linear mixed model analysis was performed to calculate intra- and interindividual variability and to assess the effects of age, sex, weight, height, weight*height as a proxy for body size, and body mass index (BMI).

Results

FGCV ranged from 0 to 156 mL, with a mean (± SD) value of 33 ± 25 mL. The overall coefficient of variation within the study population was 75.6%, interindividual SD was 15 mL, and the intraindividual SD was 19 mL. Age, weight, height, weight*height, and BMI had no effect on FGCV. Women had lower volumes compared to men (MD: -6 mL), when corrected for the aforementioned factors.

Conclusion

FGCV is highly variable, with higher intraindividual compared to interindividual variability, indicating that FGCV is subject to day-to-day and within-day variation and is not a stable personal characteristic. This highlights the importance of considering FGCV when studying digestion and drug dissolution. Exact implications remain to be studied.

GRAPHICAL ABSTRACT

KEY POINTS

Fasted gastric content volume is highly variable, both within an individual and between individuals, and should range between 0 and 138 mL in healthy young individuals.

Women have lower fasted gastric content volume compared to men; age, body weight and body size were not associated with differences in fasted gastric content volume.

Fasted gastric content volume can impact both digestion and drug dissolution, although exact implications of the observed variations remain to be studied.
Gene Sequence to 2D Vector Transformation for Virus Classification
Authors: Sanchez-Gendriz Ignacio , Azevedo Karolayne S. , de Souza Luísa C. , Dalmolin Matheus G. S. , Fernandes Marcelo A. C.
Published: March 2024

Background

DNA sequences harbor vital information regarding various organisms and viruses. The ability to analyze extensive DNA sequences using methods amenable to conventional computer hardware has proven invaluable, especially in timely response to global pandemics such as COVID-19.

Objectives

This study introduces a new representation that encodes DNA sequences in unit vector transitions in a 2D space, extracted from the 2019 repository Novel Coronavirus Resource (2019nCoVR). The main objective is to elucidate the potential of this method to facilitate virus classification using minimal hardware resources. It also aims to demonstrate the feasibility of the technique through dimensionality reduction and the application of machine learning models.

Methods

DNA sequences were transformed into two-nucleotide base transitions (referred to as ‘transitions’). Each transition was represented as a corresponding unit vector in 2D space. This coding scheme allowed DNA sequences to be efficiently represented as dynamic transitions. After applying a moving average and resampling, these transitions underwent dimensionality reduction processes such as Principal Component Analysis (PCA). After subsequent processing and dimensionality reduction, conventional machine learning approaches were applied, obtaining as output a multiple classification among six species of viruses belonging to the coronaviridae family, including SARS-CoV-2.

Results and Discussions

The implemented method effectively facilitated a careful representation of the sequences, allowing visual differentiation between six types of viruses from the Coronaviridae family through direct plotting. The results obtained by this technique reveal values accuracy, sensitivity, specificity and F1-score equal to or greater than 99%, applied in a stratified cross-validation, used to evaluate the model. The results found produced performance comparable, if not superior, to the computationally intensive methods discussed in the state of the art.

Conclusions

The proposed coding method appears as a computationally efficient and promising addition to contemporary DNA sequence coding techniques. Its merits lie in its simplicity, visual interpretability and ease of implementation, making it a potential resource in complementing existing strategies in the field.