bluuebunny/crossref_metadata_2025_split huggingface dataset:
Not all clusters are equal: dynamics of molecular HIV-1 clusters in a statewide Rhode Island epidemic
Authors: Novitsky Vlad , Steingrimsson Jon , Howison Mark , Dunn Casey W. , Gillani Fizza S. , Fulton John , Bertrand Thomas , Howe Katharine , Bhattarai Lila , Ronquillo Guillermo , MacAskill Meghan , Bandy Utpala , Hogan Joseph , Kantor Rami 
Published: January 2023

Objectives:
Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission.

Design:
Retrospective cohort.

Methods:
Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time.

Results:
Of 2153 individuals, 31% (strict criteria) – 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83–87% of all identified clusters) showed predicted growing/plateauing dynamics, with approximately three-fold higher growth rates in large (15–18%) vs. small (∼5%) clusters. Semi-normal clusters (1–2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11–16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters.

Conclusions:
Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies.
Cystatin C in addition to creatinine for better assessment of glomerular renal function decline in people with HIV receiving antiretroviral therapy
Authors: Mondesert Etienne , Reynes Jacques , Makinson Alain , Bargnoux Anne-Sophie , Plawecki Maëlle , Morquin David , Cristol Jean-Paul , Badiou Stéphanie 
Published: January 2023

Objective:
To compare the estimated glomerular filtration rate (eGFR) using the creatinine equation (eGFRcreat) or the cystatin C equation (eGFRcys) in people with HIV (PWH) under antiretroviral drugs. We specifically included patients with an eGFRcreat around 60 ml/min per 1.73 m2 to evaluate agreement on stage 2 and 3 chronic kidney disease (CKD) classification.

Design:
eGFRcreat, eGFRcys and resulting CKD staging were determined in 262 consecutive patients with HIV-1 (PWH) with a suppressed viral load (<200 copies/ml) under antiretroviral drugs and having impaired renal function (eGFRcreat between 45 and 80 ml/min per 1.73 m2). Antiretroviral drugs regimens were classified into eight groups: cobicistat (COBI)+elvitegravir (EVG), ritonavir (RTV)+protease inhibitor, dolutegravir (DTG), DTG+rilpivirine (RPV), RPV, raltegravir (RAL), bictegravir (BIC), and other antiretroviral drugs.

Results:
Mean eGFRcys was higher than mean eGFRcreat (77.7 ± 0.5 vs. 67.9  ± 7.9 ml/min per 1.73 m2, P < 0.0001). The differences were significant in five treatment groups with COBI/EVG; DTG; DTG+RPV; RPV; RAL. CKD classification was modified for 51% of patients when using eGFRcys instead of eGFRcreat, with reclassification to less severe stages in 37% and worse stages in 14%.

Conclusion:
This study highlighted significant differences in eGFR depending on the renal marker used in PWH, having a significant impact on CKD classification. eGFRcys should be an additive tool for patients having eGFRcreat around 60 ml/min per 1.73 m2 for better identification of renal impairment.
Longitudinal comparison of insulin resistance and dyslipidemia in children with and without perinatal HIV infection in South Africa
Authors: Davies Claire , Vaida Florin , Otwombe Kennedy , Cotton Mark F. , Browne Sara , Innes Steve 
Published: January 2023

Introduction:HIV infection is associated with insulin resistance and dyslipidaemia driven by HIV-associated immune dysregulation and antiretroviral therapy (ART). Children living with perinatally acquired HIV (CHIV) face many decades of exposure to these factors. We evaluated the longitudinal trajectory of insulin resistance and dyslipidaemia in CHIV and HIV-exposed uninfected children (CHEU), compared with children HIV-unexposed (CHU).Methods:Four hundred and eighty-five children (141 CHIV, 169 CHEU, 175 CHU) aged 5–16 years, previously part of CHER and P1060 trials, were followed annually at Tygerberg Children's Hospital, South Africa. The primary outcome was Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Secondary outcomes included low-density lipoprotein (LDL) cholesterol, triglyceride-to-HDL ratio, android fat mass and SBP. Outcomes were evaluated using linear mixed effects models, adjusting for potential confounders.Results:CHIV had 73% greater HOMA-IR than CHU in ages 6–8 years (95% CI 15.9–158.2%,P < 0.001), and 24.7% greater HOMA-IR than CHU in ages 9–10 years (0.3–55.1%,P = 0.04). By 10–11 years, the difference was not significant (P = 0.161). Longitudinally, triglyceride-to-HDL was 47.94% (34.50–62.73%,P < 0.001) higher in CHIV vs. CHU; LDL was 0.25 mmol/l (0.10–0.39,P = 0.001) higher in CHIV vs. CHU; android fat mass was 11.57% (−21.11 to −0.87%,P = 0.035) lower in CHIV than CHU. No significant difference in SBP was found. CHEU and CHU had similar outcomes.Conclusion:Early-treated CHIV have elevated insulin resistance, which resolves with time. Triglyceride-to-HDL ratio and LDL cholesterol were elevated into puberty. CHIV should be monitored for insulin resistance, dyslipidaemia and subclinical cardiovascular disease.
Needs for shelter or housing assistance among people with diagnosed HIV by jurisdiction: United States, 2015–2020
Authors: Dasgupta Sharoda , Beer Linda , Lu Jen-Feng , Weiser John , Yuan Xin , Nair Priya , Banks Lauren , Marcus Ruthanne 
Published: January 2023

Objective:
To describe the landscape of needs for housing assistance among people with HIV (PWH) and availability of Housing Opportunities for People with AIDS (HOPWA) funding with respect to housing service needs, nationally and for 17 US jurisdictions.

Design:
The CDC Medical Monitoring Project (MMP) is an annual, cross-sectional survey designed to report nationally and locally representative estimates of characteristics and outcomes among adults with diagnosed HIV in the United States.

Methods:
We analyzed 2015–2020 data from MMP and 2019 funding data from HOPWA. Weighted percentages and 95% confidence intervals (CIs) for national and jurisdiction-level estimates were reported.

Results:
Nationally, 1 in 4 (27.7%) PWH had shelter or housing service needs. Among those who needed housing services, 2 in 5 (40.4%) did not receive them (range: 21.3% in New York to 62.3% in Georgia). Reasons for unmet needs were multifactorial and varied by jurisdiction. Available 2019 HOPWA funding per person in need would cover up to 1.24 months of rent per person nationally (range: 0.53 months in Virginia to 9.54 months in Puerto Rico), and may not have matched housing assistance needs among PWH in certain jurisdictions.

Conclusion:
Addressing housing service needs necessitates a multipronged approach at the provider, jurisdiction, and national level. Locally, jurisdictions should work with their partners to understand and address housing service needs among PWH. Nationally, distribution of HOPWA funding for housing services should be aligned according to local needs; the funding formula could be modified to improve access to housing services among PWH.
The role of oncology pharmacists and comprehensive medication reconciliation in informing treatment plans for older adults with cancer and downstream outcomes
Authors: Whitman Andrew , Fitch Emily , Nightingale Ginah 
Published: January 2023

Purpose of review
Proper medication management is an essential part of older adult cancer care. An aging population, an increase in anticancer treatment options, and high rates of comorbid conditions make navigating general medication reconciliation complicated. This review will highlight the recent literature describing the roles of the oncology pharmacist in caring for older adults with cancer.

Recent findings
The body of literature highlighting oncology pharmacist roles in this population is mainly focused on polypharmacy and potentially inappropriate medication assessments, deprescribing nonessential therapies, drug–drug interaction reviews, and immunization optimization. Outcomes associated with oncology pharmacist interventions are still lacking as well as the development of benchmarks for appropriate pharmacy-based care in the older adult oncology population.

Summary
Oncology pharmacist interventions in older adults with cancer have the potential to improve patient care. Future randomized studies in this area of practice are warranted in order to clearly define the optimal impact of oncology pharmacists.
Immunotherapy for older patients with cancer
Authors: Araujo Vargas Tatianny P. , Al-Humiqani Abdullah , Giffoni De Mello Morais Mata Danilo , Menjak Ines B. 
Published: January 2023

Purpose of the review
The aim of this review is to describe the clinical use and tolerability of immune checkpoint inhibitors in older adults with solid tumors, where there is an abundance of evidence with recent updates including subgroups of older patients.

Recent findings
Studies with updated analyses and subgroups of older patients show that in general older patients benefit as well as younger patients and tolerate immunotherapy very well. However, in some instances of combination therapies which may expose patients to more toxicity, the benefits are reduced, and careful selection of older patients, including adjunctive assessments such as geriatric assessment, can help to identify the appropriate treatment for an individual patient.

Summary
Older adults remain underrepresented in clinical trials, including those involving immunotherapy. Therefore, efforts must be made to include more older patients in trials and to assess real-world evidence to inform decision-making.
A shift from simple to sophisticated: using intensity-modulated radiation therapy in conventional nonstereotactic palliative radiotherapy
Authors: Dennis Kristopher , Linden Kelly , Gaudet Marc 
Published: January 2023

Purpose of review
The authors aimed to highlight trends in, and evidence underlying the use of highly conformal radiotherapy (RT) techniques in conventional nonstereotactic palliative RT. The authors reviewed palliative-intent and curative-intent studies relevant to the use of intensity-modulated radiation therapy (IMRT) for the delivery of nonstereotactic conventional regimens to the brain, head and neck, thorax, abdomen and pelvis, and bone metastases.

Recent findings
The use of IMRT has become standard with certain indications for brain metastases such as hippocampus-avoiding/limiting whole brain RT. IMRT in the treatment of bone metastases is increasing at many institutions despite limited data comparing its effectiveness with that of fluoroscopy-based and three-dimensional conformal radiation therapy techniques. There is scant data describing the use of IMRT for palliation in other extracranial anatomic sites; guidance for its use in these settings must be gleaned almost exclusively from curative-intent randomized trials, consensus recommendations and contouring atlases.

Summary
Consistent with historical technology shifts in RT practice, the uptake of highly conformal techniques such as IMRT for conventional palliative RT will likely outpace rigorous evaluations of their advantages and disadvantages relative to simpler techniques. Opportunities exist in virtually all anatomic sites for observational and randomized studies to evaluate the clinical impacts of these modern techniques in the palliative setting.
Estradiol provokes hypercoagulability and affects fibrin biology: A mechanistic exploration of sex dimorphisms in coagulation
Authors: Coleman Julia R. , Moore Ernest E. , Schmitt Lauren , Hansen Kirk , Dow Nathan , Freeman Kalev , Cohen Mitchell J. , Silliman Christopher C. 
Published: January 2023

BACKGROUND
Sex dimorphisms in coagulation are well established, with female-specific hypercoagulability conferring a survival benefit in the setting of trauma-induced coagulopathy (TIC). The mechanism behind these phenomena remains to be elucidated. We hypothesize that estradiol provokes a hypercoagulable profile and alters clot proteomics and fibrin crosslinking.

METHODS
Whole blood was collected from healthy adult volunteers (n = 30). A battery of thrombelastography (TEG) assays (native, kaolin, platelet-mapping, functional fibrinogen), whole blood thrombin generation, proteomics, and clot structure architecture (via analysis of fibrin crosslinks and fluorescent fibrinogen-visualized clots) were performed after pre-treatment of the blood with physiologic concentrations of beta-estradiol. In addition, a prospective study of coagulation through the menstrual cycle was conducted by collecting blood from women on peak and nadir estrogen days in the standard 28-day menstrual cycle.

RESULTS
On TEG, in females, estradiol provoked a hypercoagulable phenotype, specifically a shorter time to clot formation and greater thrombin generation, greater rate of clot propagation and functional fibrinogen, higher clot strength, and diminished clot fibrinolysis. In both males and females, estradiol increased platelet hyperactivity. Similar changes were seen in time to clot formation and clot strength in vivo during peak estrus of the menstrual cycle. On proteomic analysis, in both males and females, estradiol was associated with increases in abundance of several procoagulant and antifibrinolytic proteins. Crosslinking mass spectrometry analysis showed addition of estradiol increased the abundance of several FXIII crosslinks within the FIBA alpha chain in both sexes. Fluorescent fibrinogen analysis revealed a trend toward increased fiber resolvability index after addition of estradiol.

CONCLUSION
Estradiol provokes a hypercoagulable phenotype, affecting time to clot formation, clot propagation, clot strength, clot fibrinolysis, and clot structure. In sum, these data highlight the role of estradiol is driving female-specific hypercoagulability and highlights its potential role as a therapeutic adjunct in resuscitation of TIC.
Surgical stabilization of critical abdominal injuries in a mature rural trauma system: A retrospective study
Authors: Tinsman Chandler , Lilienthal Michele , Galet Colette , Torner James , Skeete Dionne A. 
Published: January 2023

BACKGROUND
Worse outcomes following injuries are more likely in rural versus urban areas. In 2001, our state established an inclusive trauma system to improve mortality. In 2015, the trauma system had a consultation visit from the American College of Surgeons' Committee on Trauma, who made several recommendations. We hypothesized that continued maturation of this system would lead to more laparotomies prior to transfer to a higher level of care and better outcomes.

METHODS
Our trauma registry was queried to identify all patients transferred between January 1, 2010, and December 31, 2020, who underwent laparotomy either before transfer or within 4 hours of arrival. The preconsultation (2010–2015) and postconsultation periods (2016–2020) were compared. Categorical and continuous variables were compared using χ2 and Mann-Whitney U tests, respectively.

RESULTS
We included 213 patients; 63 had laparotomy before transfer and 150 within 4 hours after transfer. Age, injury severity scores, systolic blood pressure, and mechanism of injury were not different between periods. Proportions of laparotomy before and after transfer and outcomes (mortality, hospital length of stay, intensive care unit length of stay, ventilator days) were also similar (p = 0.368 for laparotomy, p = 0.840, 0.124, 0.286, 0.822 for outcomes). Compared with the preconsultation period, the proportion of laparotomy performed before transfer for severe injuries (abdominal Abbreviated Injury Scale score >3) significantly increased postconsultation (57.1% vs. 30.6%, p = 0.011). Incidence of damage-control laparotomies (43.9% vs. 23.6%; p = 0.020) and transfusion of plasma and platelets (33.6% vs. 13.2%; p < 0.001, 22.4% vs. 8.5%, p = 0.007, respectively) significantly increased.

CONCLUSION
Identification and surgical stabilization of critical patients at the non-Level I facilities prior to transfer, as well as blood product use and damage-control techniques, improved postconsultation, suggesting a shift in the approaches to surgical stabilization and resuscitation efforts in our trauma system.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Induction Immunosuppression Does Not Worsen Tumor Recurrence After Liver Transplantation for Hepatocellular Carcinoma
Authors: Durkin Claire , Schaubel Douglas E. , Xu Yuwen , Mahmud Nadim , Kaplan David E. , Abt Peter L. , Bittermann Therese 
Published: January 2023

Background.
Prior studies are inconsistent regarding the impact of antibody induction therapy on outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC).

Methods.
Adults transplanted with HCC exception priority were identified from February 27, 2002, to March 31, 2019, using the United Network for Organ Sharing database. Time-to-event analyses evaluated the association of antibody induction therapy (none, nondepleting induction [NDI], depleting induction [DI]) with overall post-LT patient survival and HCC recurrence. Separate multivariable models adjusted for tumor characteristics on either last exception or on explant. The interaction of induction and maintenance regimen at LT discharge was investigated.

Results.
Among 22 535 LTs for HCC, 17 688 (78.48%) received no antibody induction, 2984 (13.24%) NDI, and 1863 (8.27%) DI. Minimal differences in patient and tumor characteristics were noted between induction groups, and there was significant center variability in practices. NDI was associated with improved survival, particularly when combined with a calcineurin inhibitor (CNI) and antimetabolite (hazard ratio [HR] 0.73 versus no induction plus 3-drug therapy in the last exception model [P < 0.001]; HR 0.64 in the explant model [P = 0.011]). The combination of DI with CNI alone was also protective (HR 0.43; P = 0.003). Neither NDI nor DI was associated with tumor recurrence (all P > 0.1). However, increased HCC recurrence was observed with no induction plus CNI monotherapy (HR 1.47, P = 0.019; versus no induction plus 3-drug therapy).

Conclusions.
In conclusion, induction immunosuppression was not associated with worse post-LT outcomes in patients transplanted with HCC exception priority. An improvement in survival was possibly observed with NDI.
Shift from a Simplified to Complex Gut Microbiota Reduces Adenoma Burden in a Preclinical Rat Model of Colon Cancer
Authors: Busi Susheel Bhanu , Davis Daniel , Moskowitz Jacob , Amos-Landgraf James 
Published: January 2023

AbstractSpecific bacterial taxa in the gastrointestinal tract have been strongly associated with cases of colorectal cancer (CRC) cancer in familial adenomatous polyposis and spontaneous disease cases in humans. This has been recapitulated in animal models of CRC with positive correlations with many commensals and pathogens. However, many of these studies are performed either in germ-free animals or employ an antibiotic regime, overlooking the complex interactions of the commensals within the colon. To simplify the challenges associated with the complexity of the microbiota in the GI tract we established the Pirc rat model of colon cancer on an Altered Schaedler Flora (ASF) gut microbiota (GM), maintained in a barrier room. To elucidate the role of the simplified (ASF) and conventional GMs on disease susceptibility, We conventionalized ASF Pirc littermates. We found that the conventionalized F1 rats had increased microbial diversity and decreased colonic adenoma multiplicity. Our findings show that the complexity and the interactions of the GM community and not aFirmicutestoBacteroidetesratio are an important factor affecting disease susceptibility.
Survey of National Practices for Postgraduate Year Two Critical Care and Emergency Medicine Pharmacy Residency Emergency Response Training
Authors: Philips Eli , Cycz Clare , Liu Ji T. , Eche I. Mary , Wong Adrian 
Published: January 2023

ABSTRACTIntroductionMedical emergency response within the hospital involves an interdisciplinary team, including pharmacists. Pharmacist involvement in these teams has increased over time due to published benefits of their involvement. Development of emergency response skills may start during pharmacy residency, although limited data suggest how this is best implemented.ObjectivesLimited data evaluate post-graduate year 2 (PGY2) pharmacy resident training for emergency response, as well as PGY2 program values for this in screening/ranking candidates. A survey may help PGY2 programs improve their own programs and allow post-graduate year one (PGY1) pharmacy residents to identify residency programs that are a good fit for their career goals.MethodsA list of PGY2 critical care (CC) and emergency medicine (EM) programs were identified. The questionnaire included program demographics, characteristics of PGY2 emergency response training, and PGY2 residency program values of PGY1 emergency response exposure for screening and ranking applicants for their programs. A Fisher’s exact test was used to compare differences between CC and EM programs for these outcomes.ResultsA total of 85 complete responses were analyzed (response rate: CC = 36.4%; EM = 32.1%). Emergency response training was often with both core and longitudinal experiences (72.9%), although differed by type of programs (p<0.001). Both CC and EM programs considered PGY1 pharmacy resident exposure to emergency response in screening candidates (33.9% and 57.7%, respectively), as well as ranking candidates (22% and 38.5%, respectively). For CC programs, both Advanced Cardiovascular Life Support certification and quantity of PGY1 emergency response ranked as the most important characteristics, while EM programs ranked quantity as the most important.ConclusionThe results of this survey indicate heterogeneity in PGY2 CC and EM emergency response training. PGY1 applicants for these programs should consider their experience with emergency response as a factor in identifying an appropriate program for their initial training.