bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postdiagnosis BMI Change Is Associated with Non–Small Cell Lung Cancer Survival
Authors: Yuan Qianyu , Du Mulong , Loehrer Elizabeth , Johnson Bruce E. , Gainor Justin F. , Lanuti Michael , Li Yi , Christiani David C. 
Published: November 2021

Abstract

Background:
Body mass index (BMI) change after a lung cancer diagnosis has been associated with non–small cell lung cancer (NSCLC) survival. This study aimed to quantify the association based on a large-scale observational study.

Methods:
Included in the study were 7,547 patients with NSCLC with prospectively collected BMI data from Massachusetts General Hospital and Brigham and Women's Hospital/Dana-Farber Cancer Institute. Cox proportional hazards regression with time-dependent covariates was used to estimate effect of time-varying postdiagnosis BMI change rate (% per month) on overall survival (OS), stratified by clinical subgroups. Spline analysis was conducted to quantify the nonlinear association. A Mendelian Randomization (MR) analysis with a total of 3,495 patients further validated the association.

Results:
There was a J-shape association between postdiagnosis BMI change and OS among patients with NSCLC. Specifically, a moderate BMI decrease [0.5–2.0; HR = 2.45; 95% confidence interval (CI), 2.25–2.67] and large BMI decrease (≥2.0; HR = 4.65; 95% CI, 4.15–5.20) were strongly associated with worse OS, whereas moderate weight gain (0.5–2.0) reduced the risk for mortality (HR = 0.78; 95% CI, 0.68–0.89) and large weight gain (≥2.0) slightly increased the risk of mortality without reaching statistical significance (HR = 1.10; 95% CI, 0.86–1.42). MR analyses supported the potential causal roles of postdiagnosis BMI change in survival.

Conclusions:
This study indicates that BMI change after diagnosis was associated with mortality risk.

Impact:
Our findings, which reinforce the importance of postdiagnosis BMI surveillance, suggest that weight loss or large weight gain may be unwarranted.
Triple Targeting of Breast Tumors Driven by Hormonal Receptors and HER2
Authors: Shagisultanova Elena , Crump Lyndsey S. , Borakove Michelle , Hall Jessica K. , Rasti Aryana R. , Harrison Benjamin A. , Kabos Peter , Lyons Traci R. , Borges Virginia F. 
Published: November 2021

Abstract
Breast cancers that express hormonal receptors (HR) and HER2 display resistance to targeted therapy. Tumor-promotional signaling from the HER2 and estrogen receptor (ER) pathways converges at the cyclin D1 and cyclin-dependent kinases (CDK) 4 and 6 complex, which drives cell-cycle progression and development of therapeutic resistance. Therefore, we hypothesized that co-targeting of ER, HER2, and CDK4/6 may result in improved tumoricidal activity and suppress drug-resistant subclones that arise on therapy. We tested the activity of the triple targeted combination therapy with tucatinib (HER2 small-molecule inhibitor), palbociclib (CKD4/6 inhibitor), and fulvestrant (selective ER degrader) in HR+/HER2+ human breast tumor cell lines and xenograft models. In addition, we evaluated whether triple targeted combination prevents growth of tucatinib or palbociclib-resistant subclones in vitro and in vivo. Triple targeted combination significantly reduced HR+/HER2+ tumor cell viability, clonogenic survival, and in vivo growth. Moreover, survival of HR+/HER2+ cells that were resistant to the third drug in the regimen was reduced by the other two drugs in combination. We propose that a targeted triple combination approach will be clinically effective in the treatment of otherwise drug-resistant tumors, inducing robust responses in patients.
ОСОБЛИВОСТІ РЕАЛІЗАЦІЇ «ФЕНОМЕНУ ГІПОТЕНЗИВНОЇ ДІЇ ГЕСТАЦІЙНОГО ПРОЦЕСУ» У ВАГІТНИХ З ІДІОПАТИЧНОЮ АРТЕРІАЛЬНОЮ ГІПОТЕНЗІЄЮ
Authors: Маркін Л. Б. , Попович О. І. , Попович А. І. 
Published: November 2021

Мета дослідження – визначити провідні прояви «феномену гіпотензивної дії вагітності» у жінок з ідіопатичною артеріальною гіпотензією (ІАГ).
Матеріали та методи. Проведено оцінку центральної гемодинаміки за допомогою біоімпедансометрії з використанням аналізатора показників кровообігу АПК-01 та доплерометричне дослідження матково-плацентарного кровотоку в маткових артеріях (МА) у 50 вагітних з ІАГ і 32 вагітних із нормальним артеріальним тиском (АТ) у терміні 30–32 тиж. гестації. Контроль серцевої діяльності плода здійснювали за даними кардіотахограми (КТГ). Морфологічне дослідження плацент породілей проводили за стандартною методикою (забарвлення тканини гематоксиліном-еозином) з використанням світлооптичного мікроскопа «ЛОМО» із стандартними збільшеннями: ×10×20×40×100.
Результати дослідження та їх обговорення. Фізіологічне зниження АТ у 48,0 % вагітних з ІАГ супроводжувалось появою ознак «вазовагальної непритомності». Особливості клініки формувалися за участю автономної нервової системи і свідчили про вегетативний дисбаланс у вагітних з ІАГ. Дослідження показників центральної гемодинаміки у вагітних з ІАГ виявило у 22,0 % випадків достовірне зниження таких об᾽ємних показників кровообігу, як УО та ХО серця, що стало тригером зниження перфузії органів і тканин і, як наслідок, порушення матково-плацентарного кровотоку. Доплерометричне дослідження показників кровотоку в МА виявило помірне збільшення пульсаційного індексу (ПІ) у 28,0 % вагітних з ІАГ; показники судинної резистентності МА були вищими в середньому на 19,0 %, ніж у групі контролю. Недостатнє постачання плацентарної тканини оксигенованою кров᾽ю зумовлювало розвиток компенсованого фетального дистресу у 18,0 % вагітних з ІАГ. Морфологічна картина плацент підтверджувала наявність хронічної плацентарної дисфункції у породілей з ІАГ у вигляді деструкції значної кількості паренхіматозних елементів і реологічних порушень у міжворсинчастому просторі.
Висновки. Надання допомоги вагітним з ІАГ передбачає урахування ефекту «гіпотензивної дії вагітності», організацію ефективного моніторингу перебігу гестаційного процесу.
ВМІСТ ВІТАМІНУ D У ЖІНОК РЕПРОДУКТИВНОГО ВІКУ, ХВОРИХ НА СУБКЛІНІЧНИЙ ГІПОТИРЕОЗ
Authors: Франчук М. О. , Франчук О. А. , Кумпаненко Я. О. , Корда І. В. 
Published: November 2021

Мета дослідження – визначення дефіциту вітаміну D у жінок репродуктивного віку з вперше діагностованим субклінічним гіпотиреозом, а також встановлення взаємозв’язку між дефіцитом вітаміну D та автоімунною тиреоїдною патологією (автоімунний тиреоїдит, субклінічний гіпотиреоз) і призначення до курсу лікування вітаміну D.
Матеріали та методи. Під наглядом перебували 25 пацієнток віком від 16 до 35 років. У 20 із них діагностовано автоімунний тиреоїдит і в 5 – гіпоплазію щитоподібної залози. Підтвердження діагнозу субклінічного гіпотиреозу полягало в наявності у крові жінок нормального рівня тиреоїдних гормонів вТ3 і вТ4 та підвищеного рівня ТТГ. За стандартною методикою УЗД проводили вимірювання об’єму і оцінку структури щитоподібної залози, а також визначали рівень вітаміну D в сироватці крові цих пацієнток.
Результати дослідження та їх обговорення. Всім жінкам із субклінічним гіпотиреозом протягом 3-х місяців призначали L-тироксин у дозі 25–37,5 мкг/добу та вітамін D – Аквадетрим 6 кр./добу, а пацієнткам з АІТ ще додатково Лізорм 30 кр./двічі на день. У всіх пацієнток після лікування нормалізувався рівень ТТГ. У жінок з гіпоплазією щитоподібної залози рівень вітаміну D повернувся до норми, а у жінок з підвищенням антитіл до ТПО – незначно.
Висновки. Жінкам репродуктивного віку із субклінічним гіпотиреозом до курсу лікування необхідно додавати препарати вітаміну D задля покращення ефективності терапії.
Optimal Methods for Reducing Proxy-Introduced Bias on Patient-Reported Outcome Measurements for Group-Level Analyses
Authors: Lapin Brittany , Thompson Nicolas , Schuster Andrew , Katzan Irene L. 
Published: November 2021

Background:
Caregivers, or proxies, often complete patient-reported outcomes (PROs) on behalf of patients; yet, research has demonstrated proxies rate patient outcomes worse than patients rate their own outcomes. To improve interpretability of PROs in group-level analyses, our study aimed to identify optimal approaches for reducing proxy-introduced bias in the analysis of PROs.

Methods:

Data were simulated based on 200 patients with stroke and their proxies who both completed 9 PROMIS domains as part of a cross-sectional study. The sample size was varied as 50, 100, 200, and 500, and the proportion of patients with proxy-respondents was varied as 10%, 20%, and 50%. Six methods for handling proxy-completions were investigated: (1) complete case analysis; (2) proxy substitution; (3) Method 2 plus proxy adjustment; (4) Method 3 including inverse-probability of treatment weighting; (5) multiple imputation; (6) linear equating. These methods were evaluated by comparing average bias in PROMIS
T
-scores (estimated versus observed patient-only responses), as well as by comparing estimated regression coefficients to models using patient-only responses.

Results:

Overall mean
T
-score differences ranged from 0 to 1.75. The range of mean differences varied by the 6 methods with methods 1 and 5 providing estimates closest to the observed mean. In regression models, all but inverse-probability of treatment weighting resulted in low bias when proxy-completions were 10% to 20%. With 50% proxy-completions, method 5 resulted in less accurate estimations while methods 1 to 3 provided less proxy-introduced bias. Bias remained low across domain and varying sample sizes but increased with larger percentages of proxy-respondents.

Conclusions:
Our study found modest proxy-introduced bias when estimating PRO scores or regression estimates across multiple domains of health. This bias remained low, even when sample size was 50 and there were large proportions of proxy-completions. While many of these methods can be chosen for including proxies in stroke PRO research with <20% proxy-respondents, proxy substitution with adjustment resulted in low bias with 50% proxy-respondents.
Ankle‐Brachial Index and Subsequent Risk of Severe Ischemic Leg Outcomes: The ARIC Study
Authors: Paskiewicz Amy , Wang Frances M. , Yang Chao , Ballew Shoshana H. , Kalbaugh Corey A. , Selvin Elizabeth , Salameh Maya , Heiss Gerardo , Coresh Josef , Matsushita Kunihiro 
Published: November 2021

Background
Ankle‐brachial index (ABI) is used to identify lower‐extremity peripheral artery disease (PAD). However, its association with severe ischemic leg outcomes (eg, amputation) has not been investigated in the general population.

Methods and Results
Among 13 735 ARIC (Atherosclerosis Risk in Communities) study participants without clinical manifestations of PAD (mean age, 54 [SD, 5.8] years; 44.4% men; and 73.6% White) at baseline (1987–1989), we quantified the prospective association between ABI and subsequent severe ischemic leg outcomes, critical limb ischemia (PAD with rest pain or tissue loss) and ischemic leg amputation (PAD requiring amputation) according to discharge diagnosis. Over a median follow‐up of ≈28 years, there were 221 and 129 events of critical limb ischemia and ischemic leg amputation, respectively. After adjusting for demographics, ABI ≤0.90 versus 1.11 to 1.20 had a ≈4‐fold higher risk of critical limb ischemia and ischemic leg amputation (hazard ratios, 3.85 [95% CI, 2.09–7.11] and 4.39 [95% CI, 2.08–9.27]). The magnitude of the association was modestly attenuated after multivariable adjustment (hazard ratios, 2.44 [95% CI, 1.29–4.61] and 2.72 [95% CI, 1.25–5.91], respectively). ABI 0.91 to 1.00 and 1.01 to 1.10 were also associated with these severe leg outcomes, with hazard ratios ranging from 1.7 to 2.0 after accounting for potential clinical and demographic confounders. The associations were largely consistent across various subgroups.

Conclusions
In a middle‐aged community‐based cohort, lower ABI was independently and robustly associated with increased risk of severe ischemic leg outcomes. Our results further support ABI ≤0.90 as a threshold diagnosing PAD and also suggest the importance of recognizing the prognostic value of ABI 0.91 to 1.10 for limb prognosis.
Distinct Effects of Ibrutinib and Acalabrutinib on Mouse Atrial and Sinoatrial Node Electrophysiology and Arrhythmogenesis
Authors: Tuomi Jari M. , Bohne Loryn J. , Dorey Tristan W. , Jansen Hailey J. , Liu Yingjie , Jones Douglas L. , Rose Robert A. 
Published: November 2021

Background
Ibrutinib and acalabrutinib are Bruton tyrosine kinase inhibitors used in the treatment of B‐cell lymphoproliferative disorders. Ibrutinib is associated with new‐onset atrial fibrillation. Cases of sinus bradycardia and sinus arrest have also been reported following ibrutinib treatment. Conversely, acalabrutinib is less arrhythmogenic. The basis for these different effects is unclear.

Methods and Results

The effects of ibrutinib and acalabrutinib on atrial electrophysiology were investigated in anesthetized mice using intracardiac electrophysiology, in isolated atrial preparations using high‐resolution optical mapping, and in isolated atrial and sinoatrial node (SAN) myocytes using patch‐clamping. Acute delivery of acalabrutinib did not affect atrial fibrillation susceptibility or other measures of atrial electrophysiology in mice in vivo. Optical mapping demonstrates that ibrutinib dose‐dependently impaired atrial and SAN conduction and slowed beating rate. Acalabrutinib had no effect on atrial and SAN conduction or beating rate. In isolated atrial myocytes, ibrutinib reduced action potential upstroke velocity and Na
+
current. In contrast, acalabrutinib had no effects on atrial myocyte upstroke velocity or Na
+
current. Both drugs increased action potential duration, but these effects were smaller for acalabrutinib compared with ibrutinib and occurred by different mechanisms. In SAN myocytes, ibrutinib impaired spontaneous action potential firing by inhibiting the delayed rectifier K
+
current, while acalabrutinib had no effects on SAN myocyte action potential firing.

Conclusions
Ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function that provide insight into the basis for increased atrial fibrillation susceptibility and SAN dysfunction with ibrutinib, but not with acalabrutinib.
A new species of Tritodynamia (Brachyura, Macrophthalmidae) from Papua, Indonesia
Authors: Rahayu Dwi Listyo , Ng Peter K. L. 
Published: November 2021

Abstract
Tritodynamia nontjii n. sp. is described from Papua, Indonesia, and is distinguished from congeners by its proportionately broader carapace and relatively shorter ambulatory legs. The new species superficially resembles T. yeoi Naruse & Ng, 2010, from Singapore, in having the male first gonopod stout with the distal portion broad and curved, but the two species differ in the proportion of the carapace and structures of the ambulatory legs. A table of morphological differences of all known species of Tritodynamia is also provided to distinguish the taxa.
Seasonal and interannual variability in the density of the postlarvae of Litopenaeus setiferus and Farfantepenaeus duorarum in Términos Lagoon, Gulf of Mexico
Authors: Gómez-Ponce Mario A. , Coria-Monter Erik , Flores-Coto Cesar , Canales-Delgadillo Julio C. , Cardoso-Mohedano José G. , Durán-Campos Elizabeth 
Published: November 2021

Abstract
White shrimps, Litopenaeus setiferus (Linnaeus, 1767) and pink shrimps, Farfantepenaeus duorarum (Burkenroad, 1939) are two pivotal species in the southern Gulf of Mexico, due to their ecological and economic importance. In this study we present observational evidence of the seasonal and interannual variability of both species in the Términos Lagoon (southern Gulf of Mexico). The results suggest that the hydrography of the water column and the surface circulation exert a strong influence on the density of both species. The results presented here contribute to a better understanding of the dynamics of both species and highlight the need to combine different methodologies to achieve a better interpretation of this system.
Biosurveillance of Drug Overdoses and Substance Misuse Treated in Selected Emergency Departments in Minnesota, 2017-2020
Authors: Wiens Terra , Bilden Elisabeth , Saravia Stefan , Peterson Jason , Wogen Matthew , Hanson Kaila , Makhtal Roon , Wright Nate , Roesler Jon , Lynfield Ruth 
Published: November 2021

Objectives Increasing knowledge about the toxicology of drug overdose and substance misuse (DOSM) is important in improving our understanding of the epidemic. We describe the Minnesota Drug Overdose and Substance Use Pilot Surveillance Activity, which started collecting data on emergency department (ED) visits attributable to DOSM in 2017, with a focus on the toxicology results of a subset of clinical encounters. Methods From November 1, 2017, through January 30, 2020, we collected near–real-time data on DOSM-related ED encounters. The Minnesota Department of Health Public Health Laboratory tested leftover clinical specimens (blood and/or urine) for the presence of various substances for patients who died, were hospitalized, had an atypical clinical presentation, or were part of a local drug overdose cluster. Testing looked for >250 drugs or their metabolites, including those commonly misused (eg, methamphetamine, cocaine), prescription medications, synthetic cannabinoids and cathinones, and opioids. We describe characteristics of the overall group and a subgroup of clinical encounters with toxicology results. Results Specimens submitted from 6 EDs during the study period represented 239 clinical encounters. Methamphetamine was the most frequently detected substance (67.4%) but was suspected in only 45.6% of encounters. At least 1 opioid was detected in 42.5% of encounters but suspected in only 29.7%. Testing also detected potential adulterants and additives (eg, fentanyl, fentanyl analogues, levamisole) and showed frequent patient exposure to substances not reported by patients or suspected by clinicians. Nearly half (44.4%) of clinical encounters had >1 substance detected. Conclusions ED surveillance for DOSM encounters, enhanced by toxicology testing, can provide local situational awareness on overdoses, prevent potential mischaracterization of the true drug overdose epidemic, and inform harm reduction and drug overdose prevention efforts.
Development and Validation of a Syndrome Definition for Suspected Nonfatal Unintentional/Undetermined Intent Stimulant-Involved Overdoses
Authors: Pickens Cassandra M. , Scholl Lawrence , Liu Stephen , Smith Herschel , Snodgrass Stephanie 
Published: November 2021

Objectives To monitor stimulant-involved overdose (SOD) trends, the Centers for Disease Control and Prevention (CDC) developed and evaluated the validity of a syndromic surveillance definition for suspected nonfatal, unintentional/undetermined intent stimulant-involved overdose (UUSOD). Methods We analyzed all emergency department (ED) visits in CDC’s surveillance system that met the UUSOD syndrome definition (January 2018–December 2019). We classified visits as true positive, possible, or not UUSODs after reviewing diagnosis codes and chief complaints. We first assessed whether visits were acute SODs, subsequently classifying acute SODs by intent. The percentage of true-positive UUSODs did not include intentional or possibly intentional visits. We considered all visits with UUSOD diagnosis codes to be acute SODs and reviewed them for intent. We manually reviewed and double-coded a 10% random sample of visits without UUSOD diagnosis codes using decision rules based on signs and symptoms. The overall percentage of true-positive UUSODs was a weighted average of the percentage of true-positive UUSODs based on diagnosis codes and the percentage of true-positive UUSODs determined by manually reviewing visits without codes. Results During 2018-2019, 40 045 ED visits met the syndrome definition for UUSOD. Approximately half (n = 18 793; 46.9%) of 40 045 visits had UUSOD diagnosis codes, indicating acute SOD; of these, 98.6% (n = 18 534) were true-positive UUSODs. Of 2125 manually reviewed visits without UUSOD diagnosis codes, 32.6% (n = 693) were true-positive UUSODs, 54.2% (n = 1151) were possible UUSODs, and 13.2% (n = 281) were not UUSODs. Overall, 63.6% of visits were true-positive UUSODs, 29.3% were possible UUSODs, and 7.1% were not UUSODs. Practice Implications CDC’s UUSOD definition may assist in surveillance efforts with further refinement to capture data on SOD clusters and trends.
Now for the Good News: Self-Perceived Positive Effects of the First Pandemic Wave on Romantic Relationships Outweigh the Negative
Authors: Holmberg Diane , Bell Kathryn M. , Cadman Kim 
Published: November 2021

Media attention has highlighted the COVID-19 pandemic’s negative effects on romantic relationships (e.g., increased partner aggression). The current mixed-method study also explored potential positive effects, and how the relative balance of positive versus negative effects might have changed over time during the first pandemic wave. Individuals ( N = 186) who participated in a pre-COVID study were recruited through MTurk to participate in a four-wave longitudinal follow-up, every 2 weeks from mid-April to late May 2020. Participants completed an 8-item self-report measure assessing perceived negative and positive effects of the pandemic on their romantic relationship. Multi-level models revealed that perceived positive effects were substantially higher than perceived negative effects at each timepoint, even amongst those who reported being more heavily impacted by the pandemic. Both positive and negative effects were stable across time. Open-ended questions at the final time point were coded for common themes. Positive themes were more frequent than negative themes. The most common negative theme centered on increased stress or tension in the relationship, while the most common positive theme discussed the importance of focusing on and appreciating the relationship, including taking advantage of the gift of increased time together the pandemic had brought. Amongst all of the pandemic’s bad news, it is refreshing to consider the possibility of pandemic-related benefits for people’s romantic relationships.
Retrospective assessment of chemotherapy/biotherapy toxicity in a Hispanic/Latinx population versus published study population
Authors: Leidy Sara B , Hull Lauren R , Macik Monica R , Gonzalvo Jasmine D , Weddle Kellie J 
Published: November 2021

Introduction Eskenazi Health in Indianapolis, Indiana, USA. services diverse communities in Central Indiana, including the Hispanic/Latinx community. It has been postulated that this population experiences toxicities at a higher rate and with a faster onset than the general population when treated with chemotherapy or biotherapy. The published clinical trials that have evaluated chemotherapy/biotherapy efficacy and toxicity have not adequately represented the Hispanic/Latinx population. This retrospective analysis aims to analyze the incidence and severity of adverse drug events in the Hispanic/Latinx population compared to the general study population. Methods A retrospective chart review included patients reported as Hispanic/Latinx in the electronic medical record who had breast cancer, colon cancer, acute myeloid leukemia, or multiple myeloma currently receiving chemotherapy/biotherapy and/or received chemotherapy/biotherapy during the study period. Seventy-three instances of patients receiving chemotherapy/biotherapy and 46 unique patients were included in the final analysis. Results Of the 73 instances, 29 (40%) had toxicity at baseline prior to chemotherapy/biotherapy received during the study period. Of those 29 baseline toxicities, 26 (90%) of them had new toxicity during the study period. Of the 73 instances, 62 (85%) experienced toxicities during the study period. Conclusion Ethnicity has a proven effect on medication efficacy and safety, but the specific impact of ethnicity on chemotherapy/biotherapy toxicity risk has not been well elucidated. This study found that a majority (85%) of Hispanic/Latinx patients treated with chemotherapy/biotherapy experienced toxicity of any grade, and the majority (90%) patients who had prior toxicity experienced another toxicity.