bluuebunny/crossref_metadata_2025_split huggingface dataset:
The harm of class imbalance corrections for risk prediction models: illustration and simulation using logistic regression
Authors: van den Goorbergh Ruben , van Smeden Maarten , Timmerman Dirk , Van Calster Ben 
Published: June 2022

Abstract

Objective
Methods to correct class imbalance (imbalance between the frequency of outcome events and nonevents) are receiving increasing interest for developing prediction models. We examined the effect of imbalance correction on the performance of logistic regression models.

Material and Methods
Prediction models were developed using standard and penalized (ridge) logistic regression under 4 methods to address class imbalance: no correction, random undersampling, random oversampling, and SMOTE. Model performance was evaluated in terms of discrimination, calibration, and classification. Using Monte Carlo simulations, we studied the impact of training set size, number of predictors, and the outcome event fraction. A case study on prediction modeling for ovarian cancer diagnosis is presented.

Results
The use of random undersampling, random oversampling, or SMOTE yielded poorly calibrated models: the probability to belong to the minority class was strongly overestimated. These methods did not result in higher areas under the ROC curve when compared with models developed without correction for class imbalance. Although imbalance correction improved the balance between sensitivity and specificity, similar results were obtained by shifting the probability threshold instead.

Discussion
Imbalance correction led to models with strong miscalibration without better ability to distinguish between patients with and without the outcome event. The inaccurate probability estimates reduce the clinical utility of the model, because decisions about treatment are ill-informed.

Conclusion
Outcome imbalance is not a problem in itself, imbalance correction may even worsen model performance.
Increased Repellent Effect of DEET on Aedes aegypti (Diptera: Culicidae) Field Population
Authors: Maia Pollyana Conceição Romão , La Corte Roseli , Pires Liandra Brasil , Banfield Lydia , Logan James G , Lima-Camara Tamara Nunes 
Published: June 2022

Abstract
Insecticides and repellents are routinely used in Brazil because of the high rates of arbovirus transmission and the nuisance caused by mosquitoes. However, few studies have assessed the effectiveness of repellents against mosquito populations that have been under exposure to xenobiotics, mainly insecticides and repellents. This study investigated the sensitivity of a field population of Aedes aegypti (Linnaeus, 1762) from a dengue-endemic area under high insecticide pressure to N,N-diethylmethylbenzamide (DEET), the active ingredient in common repellent products. The field (Laranjeiras, Sergipe, Brazil) and laboratory (Rockefeller) populations were characterized for the presence of the Val1016Ile kdr mutation, associated with pyrethroid resistance, and locomotor activity. Repellency bioassays were performed to assess the response of the mosquitoes to human odor by exposing them to 10% DEET applied to the skin in ethanol. Samples from the field population showed higher frequency of the kdr mutation, 21.9% homozygous and 21.9% heterozygous, greater locomotor activity and greater sensitivity to DEET than the laboratory population. These results suggest increased sensitivity to DEET in field populations and a possible interaction between insecticide exposure and sensitivity to DEET.
Considerations and recommendations for assessment of plasma protein binding and drug–drug interactions for siRNA therapeutics
Authors: Humphreys Sara C , Davis John A , Iqbal Sajida , Kamel Amin , Kulmatycki Kenneth , Lao Yanbin , Liu Xiumin , Rodgers John , Snoeys Jan , Vigil Adam , Weng Yan , Wiethoff Christopher M , Wittwer Matthias B 
Published: June 2022

AbstractAt the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of guidance, preclinical development for siRNA followed a hybrid of the small molecule and biologics guidance documents. However, siRNA differs significantly from small molecules and protein-based biologics in its physicochemical, absorption, distribution, metabolism and excretion properties, and its mechanism of action. Consequently, certain reports typically included in filing packages for small molecule or biologics may benefit from adaption, or even omission, from an siRNA filing. In this white paper, members of the ‘siRNA working group’ in the IQ Consortium compile a list of reports included in approved siRNA filing packages and discuss the relevance of two in vitro reports—the plasma protein binding evaluation and the drug–drug interaction risk assessment—to support siRNA regulatory filings. Publicly available siRNA approval packages and the literature were systematically reviewed to examine the role of siRNA plasma protein binding and drug–drug interactions in understanding pharmacokinetic/pharmacodynamic relationships, safety and translation. The findings are summarized into two decision trees to help guide industry decide when in vitro siRNA plasma protein binding and drug–drug interaction studies are warranted.
Recurrent Skin and Soft Tissue Infection following Breast Reduction Surgery Caused by Gordonia bronchialis: A Case Report
Authors: Davidson Amelia L. , Driscoll Cassandra R. , Luther Vera P. , Katz Adam J. 
Published: June 2022

Summary:
The expanding knowledge of the breast microbiome and its constituents necessitates understanding of how it plays into human disease. Consideration of how to identify novel organisms in breast tissue is a topic of hot debate. We report a case of a 26-year-old woman with repeat incisional break-down and sanguinopurulent drainage who required repeat incision and drainage procedures after bilateral breast reduction. Cultures revealed no growth until 4 months postoperation when matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) revealed Gordonia bronchialis, a fastidious, slow-growing organism. To date, there are fewer than 30 reported cases of G. bronchialis infections and only one with breast involvement. Our patient required 6 weeks of amoxicillin-clavulanate therapy and frequent follow-up for symptom resolution. This case demonstrates the need for additional microbiologic data in patients with delayed, persistent infections after breast surgery.
Psychological Contributions to Symptom Provocation Testing After Concussion
Authors: Terpstra Alex R. , Louie Dennis R. , Iverson Grant L. , Yeates Keith Owen , Picon Edwina , Leddy John J. , Silverberg Noah D. 
Published: June 2022

Objective:
Following concussion, symptoms such as headache, dizziness, and fatigue may transiently worsen or reemerge with increased exertion or activity. Standardized tests have been developed to assess symptom increases following aerobic, cognitive, or vestibular/oculomotor challenge. Although neurophysiological mechanisms are proposed to underlie symptom increases following exertion, psychological factors such as anxiety and misinterpretation of normal bodily sensations may also play a role. In this study, we examined the contribution of psychological factors to symptom provocation testing outcomes.

Setting:
Two outpatient concussion clinics in British Columbia, Canada.

Participants:
Adults with persistent symptoms following concussion (N = 79; 62% women).

Design:
In a single session, participants completed self-report questionnaires measuring the psychological factors of interest and underwent symptom provocation testing including aerobic (Buffalo Concussion Bike Test; BCBT), cognitive (National Institutes of Health Toolbox-Cognition Battery; NIHTB-CB), and vestibular/oculomotor (Vestibular/Ocular Motor Screening for Concussion; VOMS) challenge.

Main Measures:
Psychological factors of interest included premorbid and current anxiety (Generalized Anxiety Disorder-7; GAD-7), catastrophizing (Pain Catastrophizing Scale-Adapted; PCS-A), fear avoidance behavior (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI), and somatization (Patient Health Questionnaire-15; PHQ-15). Our primary outcome variables were self-reported symptom change during each symptom provocation test.

Results:
We found that current anxiety (B = 0.034; 95% CI = 0.003, 0.065), symptom catastrophizing (B = 0.013; 95% CI = 0.000, 0.026), fear avoidance behavior (B = 0.029; 95% CI = 0.008, 0.050), and somatization (B = 0.041; 95% CI = 0.007, 0.075) were associated with increased symptoms during the VOMS in univariate models adjusted for time postinjury but not in a multivariable model that included all covariates. The psychological variables of interest were not significantly related to symptom change during the BCBT or NIHTB-CB.

Conclusion:
Our findings suggest that symptom provocation test failure should be interpreted with caution because it might indicate psychological maladjustment rather than lingering brain injury or incomplete neurophysiological recovery.
Stroke Family Caregiver Life Changes From the COVID-19 Pandemic
Authors: Miller Elaine T. , Stacy Kelly E. , Bakas Tamilyn 
Published: June 2022

ABSTRACT

BACKGROUND: Stroke family caregivers were already struggling with unmet needs and changes in their own lives from providing care. The COVID-19 pandemic added further stress and disruption to their lives. The purpose of this study was to describe life changes in 17 stroke family caregivers specifically resulting from the COVID-19 pandemic. METHODS: This study was conducted as a secondary data analysis from an ongoing randomized controlled clinical trial testing feasibility of the Telehealth Assessment and Skill-Building Kit (TASK III). Using a multimethod design, both quantitative and qualitative data were analyzed to determine caregiver life changes. Quantitative ratings regarding life changes were obtained using 17 items adapted specifically for COVID-19 from the Bakas Caregiving Outcomes Scale. Rigorous content analysis procedures for the qualitative data were guided by a start list of codes based on the 17 items, with additional themes possible. Representative quotes were selected based on author consensus. RESULTS: Findings revealed both negative and positive life changes from the COVID-19 pandemic. Negative life changes included such things as disrupted daily routines, limited access to healthcare providers and resources (eg, food, masks, hand sanitizers), reduced family and social contact and activities, decreased emotional well-being, and problems with performing caregiving activities for the survivor. Positive life changes were increased use of the Internet and videoconferencing, closer relationships with friends, and learning how to access needed resources in new ways. CONCLUSION: Stroke family caregivers experienced both negative and positive life changes specifically as a result of the COVID-19 pandemic. Responses further indicated that COVID-19 affected most caregivers in different ways and an individualized approach is needed in dealing with caregiver life changes.
Relationship between C-reactive protein/albumin ratio and dipper/nondipper pattern in normotensive individuals
Authors: Kayikçioğlu Hatice , Akbuğa Kürşat 
Published: June 2022

ObjectiveNondipper blood pressure pattern plays an important role in cardiovascular events even in normotensive individuals. The relationship between CRP (C-reactive protein)/albumin ratio (CAR), a valuable marker of inflammation and cardiovascular diseases, has been studied for a long time. We aimed to investigate the relationship between CAR and dipper/nondipper pattern in normotensive subjects.MethodsA total of 78 dipper and 78 nondipper participants, based on ambulatory blood pressure monitoring (ABPM), were retrospectively included in our study. CAR and other parameters of all participants were collected from blood samples taken at the time of monitoring.ResultsCAR was significantly higher in the nondipper group than dipper group (P= 0.001). CAR was negatively and significantly correlated with nocturnal SBP fall ratio and nocturnal DBP fall ratio (P< 0.001). CRP/albumin ratio was found significantly and independently associated with the nondipper pattern (P= 0.002).ConclusionWe found that normotensive individuals with nondipping pattern tend to have increased CAR. Increased inflammatory response could contribute to increase in the atherosclerotic risk in nondippers compared with dippers even in a normotensive profile.
Sex difference in blood pressure response to orthostatic stress: effects of transcutaneous electrical nerve stimulation
Authors: Gomes Erika Alvarenga Corrêa , Rodrigues Gabriel Dias , Oliveira André Luiz Musmanno Branco , Velasco Larissa Lírio , Soares Pedro Paulo da Silva , Nóbrega Antonio Claudio Lucas da , Toledo-Arruda Alessandra Choqueta 
Published: June 2022

Objective
We investigated sex differences in blood pressure (BP) response to transcutaneous electrical nerve stimulation (TENS) during orthostatic stress (ORT).

Methods
Seventeen healthy young adults (males = 9; females = 8) underwent TENS or SHAM stimulus applied in the cervicothoracic region for 30 min in the supine position followed by 10 min in the orthostatic position. Electrocardiogram and BP were continuously recorded at rest and during ORT. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated from the BP signal.

Results
Orthostatic challenge decreased BP similarly for both sexes during ORT, a deeper drop in CO and a slight increase in heart rate were found in women compared with men (P = 0.03 and 0.05, respectively). TENS evoked a pronounced fall in SBP in men compared with the SHAM condition (P < 0.05). TENS has no effect on SBP in women compared with the SHAM condition.

Conclusion
This finding suggests a possible modulatory effect by one cervicothoracic TENS session on sympathetic tonus in healthy men.
Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity
Authors: Brajer-Luftmann Beata , Kaczmarek Mariusz , Nowicka Agata , Stelmach-Mardas Marta , Wyrzykiewicz Magdalena , Yasar Senan , Piorunek Tomasz , Sikora Jan , Batura-Gabryel Halina 
Published: June 2022

Abstract
The role of regulatory T cells (Tregs), damage-associated molecular patterns (DAMPs), and myeloid-derived suppressor cells (MDSCs) in the mechanism of innate and adaptive immune responses in chronic obstructive pulmonary disease (COPD) is not well understood.
Evaluating the presence of Tregs in the bronchoalveolar lavage fluid (BALF) and peripheral blood in patients with COPD, and assessment of the relationship between Tregs, MDSCs, and DAMPs as factors activating innate and adaptive immune responses. Description of the association between immune and clinical parameters in COPD.
Thirty-one patients with COPD were enrolled. Clinical parameters (forced expiratory volume in one second [FEV1], forced vital capacity, total lung capacity [TLC], diffusion capacity of carbon monoxide, and B-BMI, O-obstruction, D-dyspnea, E-exercise [BODE]) were assessed. Tregs and MDSCs were investigated in the BALF and blood using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. The levels of defensin (DEF2), galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), heat shock protein-27 (HSP27), and surfactant protein A were assessed via sandwich enzyme-linked immunosorbent assay.
The percentage of Tregs was significantly higher in the blood than in the BALF, in contrast to the mean fluorescence intensity of forkhead box P3 (FoxP3). Significant associations were observed between Tregs and HSP27 (r = 0.39), Gal-1 (r = 0.55), Gal-9 (r = −0.46), and MDSCs (r = −0.50), and between FoxP3 and Gal-1 (r = −0.42), Gal-3 (r = −0.39), and MDSCs (r = −0.43). Tregs and clinical parameters, including FEV1%pred (r = 0.39), residual volume (RV)%pred (r = −0.56), TLC%pred (r = −0.55), RV/TLC (r = −0.50), arterial oxygen saturation (r = −0.38), and arterial oxygen pressure (r = −0.39) were significantly correlated. FoxP3 was significantly interlinked with RV/TLC (r = −0.52), arterial oxygen pressure (r = 0.42), and BODE index (r = −0.57).
The interaction between innate and adaptive immune responses in patients with COPD was confirmed. The expression of Tregs in BALF may have prognostic value in patients with COPD. The conversion of immune responses to clinical parameters appears to be associated with disease severity.
Case report: pathological complete response in an IIIB non-small cell lung cancer patient after preoperative neoadjuvant nivolumab therapy combined with chemotherapy
Authors: Li Luzhen , Chen Ting , Lai Huiqin , Zhang Ao , Zhao Xianhui , Wu Jiaming , Hong Huisi , Wu Lexia , Lin Sihong , Wang Kexin , Zhang Huatang , Fang Cantu 
Published: June 2022

Abstract

Rationale:
For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer.

Patient concerns:
A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to “coughing for more than one month.”. The patient had nothing of note in either his medical history or that of his family, and no history of smoking.

Diagnosis:
The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery.

Interventions:
The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21.

Outcomes:
The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR)

Lessons:
In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.
Korean medicine registry of herbal medicine for weight loss
Authors: Ko Mi Mi , Kim Bo-Young , Son Mi Ju , Jegal Kyung Hwan , Chung Won-Seok , Kim Sungha 
Published: June 2022

Abstract

Introduction:
In South Korea, the prevalence of obesity has continuously increased over the last decade, and the burden of social and economic costs has also increased immensely. The purpose of this study is to investigate the clinical characteristics and current status of patients receiving herbal medicine (HM) treatment for weight loss in Korean medicine (KM) by constructing a multi-institutional prospective registry.

Methods and analysis:
This is a prospective, observational, multi-center registry, including patients visiting the KM clinics in South Korea for weight loss. This study will collaborate with 15 KM clinics and recruit patients into the registry between October 2021 and October 2022. The study population will include patients visiting the KM clinics for weight loss. A total of 1000 eligible patients visiting the KM clinics for weight loss who decide to undergo HM treatment will be enrolled in the registry. After enrollment, we will collect the individual characteristics of each patient, such as body mass index, body composition test, liver and kidney function tests, and information on prescribed HM. We will also record the adverse events at each visit.

Discussion:
This study is the first prospective, multicenter registry of HM for weight loss in KM clinics. The results of this registry may show the current status of patients who receive HM treatments for weight loss and provide evidence for reasonable decision-making on KM healthcare policy for obese patients in the future.
Outcomes of guideline-based medical therapy in patients with acute heart failure and reduced left ventricular ejection fraction
Authors: Jan Reem K. , Alsheikh-Ali Alawi , Mulla Arif Al , Sulaiman Kadhim , Panduranga Prashanth , Al-Mahmeed Wael , Bazargani Nooshin , Al-Suwaidi Jassim , Al-Jarallah Mohammed , Al-Motarreb Ahmed , Salam Amar , Al-Zakwani Ibrahim 
Published: June 2022

Abstract
This study aimed to report on the use, predictors and outcomes of guideline-based medical therapy (GBMT) in patients with acute heart failure (HF) with reduced ejection fraction of <40% (HFrEF), from seven countries in the Arabian Gulf.
Patients with acute HFrEF (N = 2680), aged 18 years or older, and hospitalized February–November 2012 were recruited and data were collected post discharge at 3 months (n = 2477) and 1 year (n = 2418). The use and doses of GBMT were evaluated as per European, American and Canadian HF guidelines. Analyses were performed using multivariate logistic regression. This study was registered at clinicaltrials.gov (NCT01467973).
The majority of patients were on dual (39%) and triple (39%) GBMT modalities, 14% received one GBMT medication, while 7.2% were not on any GBMT medications. On admission, 80% of patients were on renin-angiotensin system (RAS) blockers, 75% on b-blockers and 56% on mineralocorticoid receptor antagonists (MRAs), with a small proportion of these patients were taking target doses (RAS blockers 13%, b-blockers 7.3%, MRAs 14%). Patients taking triple GBMT were younger (P < .001), less likely to have comorbidities such as diabetes mellitus (P < .001) and CKD/dialysis (P < .001), less likely to receive in-hospital invasive treatments (P < .001), and more likely to be treated by a cardiologist (P < .001), than patients on a single medication. Patients taking triple GBMT showed significantly reduced all-cause mortality both at 3-months (P = .048), and at 12-months (P = .003), compared to patients taking no GBMT.
Triple GBMT prescribing and dosing in patients with HFrEF were suboptimal in the Arabian Gulf. Further studies are required to investigate GBMT utilization and dosing in the outpatient setting.
Enhanced recovery in elderly patients undergoing pancreatic resection
Authors: Scarsi Susanna , Martin David , Halkic Nermin , Demartines Nicolas , Roulin Didier 
Published: June 2022

Abstract
Enhanced recovery after surgery (ERAS) pathway for pancreas has demonstrated its value in clinical practice. However, there is a lack of specific evidence about its application in elderly patients. The aim of the present study was to assess the impact of age on compliance and postoperative outcomes. Patients ≥70 years old that underwent pancreatic resection within an ERAS pathway between 2012 and 2018 were included, and divided into three groups: 70–74, 75–79, and ≥80 years old. Compliance with ERAS items, length of stay, mortality, and complications were analyzed. 114 patients were included: 49, 37, and 28 patients aged 70–74, 75–79, and ≥80 years, respectively. Overall compliance to ERAS items between groups was not different (66%, 66%, and 62%, P = .201). No significant difference was observed in terms of median length of stay (14, 17, and 17 days, P = .717), overall complications (67%, 78%, and 71%, P = .529), major complications (26%, 32%, and 39%, P = .507), or mortality (0%, 3%, and 4%, P = .448) with increasing age. Application of an ERAS pathway is feasible in elderly patients with pancreatic resection. Increasing age was neither associated with poorer compliance nor worse postoperative outcomes.