bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Trial Diversity in Oncology: FDA Takes Action with Post–Marketing Requirements or Commitments
Authors: Kim Janice , Kester Robert , Blumenthal Gideon 
Published: November 2022

Abstract
In recent years, there has been a renewed focus on promoting the inclusion of patients from racial and ethnic minority groups in oncology clinical trials. FDA Oncology has long pointed to the underrepresentation of racial minorities in registration trials leading to approval. US FDA’s Guidance on diversity discusses how diversity could be handled within clinical trials, giving recommendations on broadening eligibility criteria, inclusive trial practices, and alternative trial designs. While there is no specific guidance from the FDA on cancer clinical trials, the recommendation is to include a representative population applicable to the US population. With the recent renewed focus on diversity in oncology clinical trials, FDA Oncology has recently asked for the completion of a Diversity Plan during drug development and has issued post–marketing commitments and requirements at the time of approval. As FDA has started to issue post–marketing requirements or commitments regarding diversity in 2020, we sought to analyze the post–marketing studies asking for a study of racial and ethnic minorities issued by the FDA’s Office of Oncologic Diseases (OOD). The analysis demonstrated the need to increase the enrollment of a diverse patient population in cancer clinical trials.
The Late Roman Colonate
Authors: Lenski Noel 
Published: November 2022

Abstract
The ‘bound colonate’ is a subject of controversy among scholars, some of whom argue that it existed as a new status between free and slave, while others feel it was merely a fiscal concern that has been exaggerated into a historiographic myth. A survey of the evidence confirms that the bound colonate grew out of fiscal registration in the late third century but then took on a life of its own as a third status of semi-servility in the following century. It had become fully articulated by the early fifth century such that the many peasants enmeshed in it were compelled to live as permanent tenants bound to the land on which they were born and burdened with numerous impediments to their freedom. The bound colonate survived intact in the eastern empire through the sixth century but was modified in various forms in the post-Roman successor states of the West.
Slave Labour and Production
Authors: Rihll T.E. 
Published: November 2022

Abstract
This chapter examines the productive work that slaves performed in antiquity, and the lifestyles typically associated with different types of endeavour. Most slaves performed a variety of functions for their owners, from helping in the fields or the yard by day to keeping house, or bed, by night. Others were specialists in jobs like digging underground, or sailing in search of fish or markets, and had little or no contact with their masters on most days of their lives. Sophisticated systems were developed to motivate slaves to work hard under minimal supervision, creating an environment in which low-status workers made high-quality products, and through which strong partnerships could be formed despite the status distinction. Some roles offered slaves engaged in them opportunities to acquire wealth and freedom, whereas some were very dangerous or unpleasant. Slaves inevitably did the jobs that anyone who could refuse would not do.
Computational Modeling of Oddball Sequence Processing Exposes Common and Differential Auditory Network Changes in First-Episode Schizophrenia-Spectrum Disorders and Schizophrenia
Authors: Todd Juanita , Howard Zachary , Auksztulewicz Ryszard , Salisbury Dean 
Published: November 2022

AbstractBackground and HypothesisDifferences in sound relevance filtering in schizophrenia are proposed to represent a key index of biological changes in brain function in the illness. This study featured a computational modeling approach to test the hypothesis that processing differences might already be evident in first-episode, becoming more pronounced in the established illness.Study DesignAuditory event-related potentials to a typical oddball sequence (rare pitch deviations amongst regular sounds) were recorded from 90 persons with schizophrenia-spectrum disorders (40 first-episode schizophrenia-spectrum, 50 established illness) and age-matched healthy controls. The data were analyzed using dynamic causal modeling to identify the changes in effective connectivity that best explained group differences.Study ResultsGroup differences were linked to intrinsic (within brain region) connectivity changes. In activity-dependent measures these were restricted to the left auditory cortex in first-episode schizophrenia-spectrum but were more widespread in the established illness. Modeling suggested that both established illness and first-episode schizophrenia-spectrum groups expressed significantly lower inhibition of inhibitory interneuron activity and altered gain on superficial pyramidal cells with the data indicative of differences in both putative N-methyl-d-aspartate glutamate receptor activity-dependent plasticity and classic neuromodulation.ConclusionsThe study provides further support for the notion that examining the ability to alter responsiveness to structured sound sequences in schizophrenia and first-episode schizophrenia-spectrum could be informative to uncovering the nature and progression of changes in brain function during the illness. Furthermore, modeling suggested that limited differences present at first-episode schizophrenia-spectrum may become more expansive with illness progression.
Linking Personalized Brain Atrophy to Schizophrenia Network and Treatment Response
Authors: Ji Gong-Jun , Zalesky Andrew , Wang Yingru , He Kongliang , Wang Lu , Du Rongrong , Sun Jinmei , Bai Tongjian , Chen Xingui , Tian Yanghua , Zhu Chunyan , Wang Kai 
Published: November 2022

Abstract

Background and Hypothesis
Schizophrenia manifests with marked heterogeneity in both clinical presentation and underlying biology. Modeling individual differences within clinical cohorts is critical to translate knowledge reliably into clinical practice. We hypothesized that individualized brain atrophy in patients with schizophrenia may explain the heterogeneous outcomes of repetitive transcranial magnetic stimulation (rTMS).

Study Design
The magnetic resonance imaging (MRI) data of 797 healthy subjects and 91 schizophrenia patients (between January 1, 2015, and December 31, 2020) were retrospectively selected from our hospital database. The healthy subjects were used to establish normative reference ranges for cortical thickness as a function of age and sex. Then, a schizophrenia patient’s personalized atrophy map was computed as vertex-wise deviations from the normative model. Each patient’s atrophy network was mapped using resting-state functional connectivity MRI from a subgroup of healthy subjects (n = 652). In total 52 of the 91 schizophrenia patients received rTMS in a randomized clinical trial (RCT). Their longitudinal symptom changes were adopted to test the clinical utility of the personalized atrophy map.

Results
The personalized atrophy maps were highly heterogeneous across patients, but functionally converged to a putative schizophrenia network that comprised regions implicated by previous group-level findings. More importantly, retrospective analysis of rTMS-RCT data indicated that functional connectivity of the personalized atrophy maps with rTMS targets was significantly associated with the symptom outcomes of schizophrenia patients.

Conclusions
Normative modeling can aid in mapping the personalized atrophy network associated with treatment outcomes of patients with schizophrenia.
Advancing digital health equity: Directions for behavioral and social science research
Authors: Jaworski Beth K , Webb Hooper Monica , Aklin Will M , Jean-Francois Beda , Elwood William N , Belis Deshirée , Riley William T , Hunter Christine M 
Published: November 2022

Abstract
The field of digital health is evolving rapidly and encompasses a wide range of complex and changing technologies used to support individual and population health. The COVID-19 pandemic has augmented digital health expansion and significantly changed how digital health technologies are used. To ensure that these technologies do not create or exacerbate existing health disparities, a multi-pronged and comprehensive research approach is needed. In this commentary, we outline five recommendations for behavioral and social science researchers that are critical to promoting digital health equity. These recommendations include: (i) centering equity in research teams and theoretical approaches, (ii) focusing on issues of digital health literacy and engagement, (iii) using methods that elevate perspectives and needs of underserved populations, (iv) ensuring ethical approaches for collecting and using digital health data, and (v) developing strategies for integrating digital health tools within and across systems and settings. Taken together, these recommendations can help advance the science of digital health equity and justice.
Data-driven discovery of canonical large-scale brain dynamics
Authors: Piccinini Juan , Deco Gustavo , Kringelbach Morten , Laufs Helmut , Sanz Perl Yonatan , Tagliazucchi Enzo 
Published: November 2022

Abstract
Human behavior and cognitive function correlate with complex patterns of spatio-temporal brain dynamics, which can be simulated using computational models with different degrees of biophysical realism. We used a data-driven optimization algorithm to determine and classify the types of local dynamics that enable the reproduction of different observables derived from functional magnetic resonance recordings. The phase space analysis of the resulting equations revealed a predominance of stable spiral attractors, which optimized the similarity to the empirical data in terms of the synchronization, metastability, and functional connectivity dynamics. For stable limit cycles, departures from harmonic oscillations improved the fit in terms of functional connectivity dynamics. Eigenvalue analyses showed that proximity to a bifurcation improved the accuracy of the simulation for wakefulness, whereas deep sleep was associated with increased stability. Our results provide testable predictions that constrain the landscape of suitable biophysical models, while supporting noise-driven dynamics close to a bifurcation as a canonical mechanism underlying the complex fluctuations that characterize endogenous brain activity.
Multiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer
Authors: Mokhtech Meriem , Miccio Joseph A. , Johung Kimberly , Cecchini Michael , Stein Stacey , Narang Amol K. , Herman Joseph M. , Kunstman John , Haddock Michael G. , Anker Christopher J. , Jabbour Salma , Hallemeier Christopher L. , Jethwa Krishan R. 
Published: November 2022

Background and Purpose:
Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC.

Methods:
Patients diagnosed with nonmetastatic PDAC between 2012 and 2017 and who received preoperative MAC or MAC+RT were identified in the National Cancer Database. Variables associated with R0 and overall survival were identified with logistic regression and Cox analysis (P<0.05).

Results:
A total of 5273 patients were identified (MAC: 3900, MAC+CRT: 955, MAC+SBRT: 418). The median RT dose/fraction (fx) in the MAC+CRT and MAC+SBRT cohorts was 50.4 Gy/28 fx and 33 Gy/5 fx. Patients receiving MAC+CRT versus MAC+SBRT had similar rates of ypT3-T4 disease (54% vs. 58%, P=0.187), R0 (87% vs. 84%, P=0.168), and pathologic complete response (pathologic complete response; 6% vs. 4%, P=0.052), however, MAC+CRT was associated with less regional lymphatic disease (ypN+: 28% vs. 41%, P<0.001). The median overall survival of patients receiving MAC+CRT versus MAC+SBRT was 24.6 versus 29.5 months (P=0.045).

Conclusions:
For patients with resected PDAC, MAC+CRT, and MAC+SBRT had similar rates of R0 and pathologic complete response, although MAC+CRT was associated with lower ypN+. Prospective evaluation of neoadjuvant RT regimens with attention to radiation therapy design is warranted.
Radiographic Response of Solitary Plasmacytomas After Conformal Radiotherapy May Be Delayed
Authors: Kosydar Samuel , Gulhane Avanti , Libby Edward , Cowan Andrew J. , Kwok Mary , Lee Sarah S. , Green Damian J. , Coffey David , Holmberg Leona A. , Chen Delphine L. , Tseng Yolanda D. 
Published: November 2022

Objective:
Although recurrence rates after radiotherapy for solitary plasmacytoma (SP) are well established, little is known about how SP responds radiographically, as most historical patients were treated in the 2D era. We evaluated the response to radiotherapy among SP patients staged and treated with 3D techniques, including proton therapy, which has not yet been previously reported.

Methods and Materials:
Between 2007 and 2021, 15 SP patients (4 extramedullary, 11 bone) staged with 3D imaging and bone marrow evaluation were consecutively treated with definitive radiotherapy. The best response was categorized in 9 evaluable patients according to response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST).

Results:
With a median follow-up of 34 months, 4 patients relapsed. The median time to the best response was ~2 years (26.6 mo RECIST, 25.4 mo PERCIST). Response rates differed based on response assessment criteria. PERCIST was associated with higher rates of complete (85.7%) or partial response (14.3%) compared with RECIST (16.7% complete, 33.3% partial). Two-year and 4-year PFS for extramedullary SP were 100% and 75%, compared with 91% and 55% for bone (P=0.75). Patients treated with proton therapy (n=5) did not appear to have different patterns of relapse (1 marginal, 1 distant) compared with those treated with photons or electrons (n=10; 2 distant).

Conclusions:
More conformal dose distribution with proton therapy does not appear to alter patterns of recurrence. Although response rates differ based on criteria by both RECIST and PERCIST assessments, the radiographic response may be slow and requires validation in other cohorts.
Changes in cardiovascular disease risk factors during menopausal transition in Japanese women: the Circulatory Risk in Communities Study (CIRCS)
Authors: Teramura Saki , Sankai Tomoko , Yamagishi Kazumasa , Umesawa Mitsumasa , Hayama-Terada Mina , Muraki Isao , Tanaka Mari , Kihara Tomomi , Ohira Tetsuya , Imano Hironori , Cui Renzhe , Shimizu Yuji , Okada Takeo , Kitamura Akihiko , Kiyama Masahiko , Iso Hiroyasu 
Published: November 2022

Abstract

Objective
We aimed to longitudinally clarify the changes in cardiovascular disease risk factors associated with menopause in Japanese women in the 2000s.

Methods
Of the 4,596 women who underwent health examinations between 2007 and 2012 in three communities of the Circulatory Risk in Communities Study, 263 women who reported going through menopause during that period were included in the study. We randomly selected 1,665 men as control subjects who participated in a health examination at least once between 2001 and 2009 and at least once between 2010 and 2018 by 1:1 pair-matching for age, community, and examination year. The health examination data from 3 to 6 years before (2001-2009) and after menopause age (2010-2018) were compared in terms of body mass index, systolic and diastolic blood pressure levels, serum total cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin A1c, hemoglobin, aspartate aminotransferase, alanine aminotransferase, and current smoker status.

Results
Compared with the men, the women showed a greater increase in serum total cholesterol (+16.7 vs −3.1 mg/dL, P < 0.001), non-high-density lipoprotein cholesterol (+15.9 vs −6.3 mg/dL, P < 0.001), fasting triglycerides (+1.2 vs +1.0 mg/dL, P = 0.027), triglycerides regardless of fasting status (+1.2 vs −0.9 mg/dL, P < 0.001), uric acid (+0.5 vs +0.2 mg/dL, P = 0.008), hemoglobin (+0.9 vs −0.3 g/dL, P < 0.001), aspartate aminotransferase (+2.9 vs −2.7 IU/L, P < 0.001), and alanine aminotransferase (+2.9 vs −2.6 IU/L, P < 0.001). No differences were found in the changes in body mass index, systolic and diastolic blood pressures, and hemoglobin A1c between the women and the matched men.

Conclusions
Menopause may be a crucial factor related to changes in serum total cholesterol, non-high-density lipoprotein cholesterol, triglycerides, uric acid, hemoglobin, and liver enzymes.
Gender Differences in Anxiety, Depression, Insomnia, and Quality of Life in Heart Failure With Preserved Ejection Fraction: A Multicenter, Cross-sectional Study
Authors: Yang Xiaoyun , Wen Yi , Peng Huiji , Zhu Hongjin , Wang Wei Eric , Zhou Jianrong 
Published: November 2022

Background
Patients with heart failure with preserved ejection fraction (HFpEF) are more often female, but gender differences in psychological distress in patients with HFpEF have not been determined.

Objective
We aimed to compare anxiety, depression, insomnia, and quality of life (QoL) between women and men with HFpEF.

Methods
A total of 263 consecutive hospitalized patients with HFpEF were enrolled in a multicenter study. Demographic and clinical characteristics were recorded. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), insomnia was assessed by the Insomnia Severity Index and Pittsburgh Sleep Quality Index, and QoL was assessed by the Kansas City Cardiomyopathy Questionnaire.

Results
Women accounted for 59% and men accounted for 41% of the patients with HFpEF. Women and men had similar New York Heart Association functional class and N-terminal pro–brain natriuretic peptide levels. Between women and men with HFpEF, similar depression prevalence (HADS-D: 4.9 ± 3.7 vs 4.1 ± 3.6, P = .222), insomnia severity (Insomnia Severity Index: 9.3 ± 6.4 vs 8.0 ± 6.5, P = .120), and QoL (Kansas City Cardiomyopathy Questionnaire: 46.6 ± 12.6 vs 47.6 ± 12.7, P = .738) were found when adjusting for potential confounders. Women had more severe anxiety (HADS-Anxiety: 2.4 ± 2.9 vs 1.6 ± 2.3, P = .025) and worse sleep quality (Pittsburgh Sleep Quality Index: 9.9 ± 4.6 vs 8.7 ± 4.5, P = .046) compared with men after adjustment.

Conclusions
There were no gender differences in depression, insomnia, and QoL in patients with HFpEF when adjusting for confounders. Women with HFpEF suffered more severe anxiety and sleep quality than men after adjustment. Thus, it is recommended that psychological distress in patients with HFpEF be assessed in clinical practice, and gender differences taken into consideration.
The role of noninvasive scoring systems for predicting cardiovascular disease risk in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis
Authors: Yi Mengshi , Peng Wei , Teng Fei , Kong Qingyan , Chen Zheyu 
Published: November 2022

Backgrounds
Cardiovascular disease (CVD) is suggested as a leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). The aim of this work was to clarify the role of noninvasive scoring systems (NSSs) in predicting CVD risk among this population.

Methods
The PubMed, Web of Science, and Cochrane databases were searched until 23 March 2022. Meta-analysis was performed for three most commonly used NSS separately, that is, fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and AST/platelet ratio index (APRI).

Results
Totally, nine studies including 155 382 patients with NAFLD were enrolled. Patients with NAFLD had a higher risk of CVD with increasing FIB-4 score (1.94, 1.52–2.46), the association remained significant after adjustment for age, sex, body mass index, hypertension, and diabetes (2.44, 1.85–3.22). Similarly, a higher risk of CVD was also observed in patients with increasing NFS (2.17, 1.58–2.98) and APRI scores (1.36, 1.04–1.79) in the unadjusted model. However, in the adjusted model, the association was significant only for NFS (3.83, 1.40–10.43), but not for APRI (1.41, 0.79–2.51). Additionally, the increment in CVD risk was most noticeable in subgroup of FIB > 2.67 vs. FIB ≤ 1.3 (6.52, 3.07–13.86) and subgroup of NFS > 0.676 vs. NFS ≤ −1.455 (16.88, 5.68–50.23). All subgroup analyses showed significant associations between FIB-4, NFS, and risk of CVD. Sensitivity analyses did not modify these results.

Conclusions
FIB-4 and NFS might be useful in identifying those who are at higher risk of CVD among patients with NAFLD. However, APRI was not recommended for this use.
Muscle Strength and Power in People With Parkinson Disease: A Systematic Review and Meta-analysis
Authors: Gamborg Mads , Hvid Lars Grøndahl , Thrue Cecilie , Johansson Sverker , Franzén Erika , Dalgas Ulrik , Langeskov-Christensen Martin 
Published: November 2022

Background and Purpose:No studies have synthesized the literature regarding mechanical muscle function (ie, strength, power, rate of force development [RFD]) in people with Parkinson disease (PD). Here, we aimed to expand our understanding of mechanical muscle function in people with PD (PwPD) by systematically reviewing (1) the psychometric properties of isokinetic/isometric dynamometry in PD, (2) the literature comparing mechanical muscle function in PwPD with healthy controls (HC), and (3) reported associations between muscle mechanical muscle function and functional capacity and/or disease severity.Methods:Systematic literature search in 6 databases. Included studies had to (1) enroll and report data on PwPD, (2) include assessment(s) of psychometric properties (ie, validity, reliability, responsiveness) of isokinetic/isometric dynamometry in PD, and/or (3) assess mechanical muscle function in both PwPD and HC using isokinetic/isometric dynamometry.Results:A total of 40 studies were included. Aim 1 studies (n = 2) showed high reliability for isometric dynamometry (hip-abductor/dorsiflexor/trunk flexor-extensor/handgrip: intraclass correlations coefficients range = 0.92-0.98). Aim 2 studies (n = 40) showed impaired mechanical muscle function (ie, strength, power, RFD) in PwPD compared with HC (effect sizes range = 0.52-1.89). Aim 3 studies (n = 11) showed weak-to-strong associations between overall and lower extremities muscle strength and functional capacity and/or disease severity outcomes (ie, Unified Parkinson Disease Rating Scale).Discussion and Conclusions:Sparse methodological evidence suggests high reliability when using dynamometry in PwPD. Muscle strength, power, and RFD are impaired in PwPD compared with HC. Muscle strength is associated with functional capacity and disease severity.Video Abstract availablefor more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A403).