bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal and Spatial Assessment of the Corneal Response to UV Cross-Linking Using 3-Dimensional In Vivo Confocal Microscopy
Authors: Parsa Shyon , Rodriguez Alejandro , Robertson Danielle M. , Bowman Robert Wayne , Petroll Walter Matthew 
Published: March 2022

Abstract:
The goal of this study was to evaluate the temporal and spatial pattern of wound healing following UV corneal cross-linking (CXL) using 3-dimensional (3-D) confocal imaging in vivo. Using a modified Heidelberg Retinal Tomograph with Rostock Corneal Module confocal microscope, we performed 3-D scans on two patients at multiple time points after CXL. Patient 1 showed a normal post-CXL wound healing response, with initial subbasal nerve loss and keratocyte apoptosis in the anterior stroma, followed by partial restoration of both the nerve plexus and stromal keratocytes by 6 months. In patient 2, in addition to anterior corneal damage, pyknotic nuclei were observed in the posterior stroma 7 days after CXL. Acellular areas were present in the posterior stroma at 3 months, with only partial keratocyte repopulation at 6 months. Regeneration of the subbasal nerve plexus was also delayed. Three-dimensional confocal imaging allowed these unusual wound healing responses to be identified in the absence of any corresponding clinical observations.
Characteristics of Higher-Order Aberrations in Different Stages of Keratoconus
Authors: Koh Shizuka , Inoue Ryota , Maeno Sayo , Mihashi Toshifumi , Maeda Naoyuki , Jhanji Vishal , Nishida Kohji 
Published: March 2022

Objectives:
To characterize higher-order aberrations (HOAs) in clinical and subclinical keratoconus (KC).

Methods:
The study included 33, 36, and 26 patients with clinical, topographic (no clinical signs), and pretopographic (normal topography and no clinical signs) KC and 30 controls. Ocular and corneal HOAs for the 4-mm pupils were measured using a wavefront sensor and expanded up to the sixth order of Zernike polynomials. The magnitudes of trefoil, coma, tetrafoil, secondary astigmatism, and spherical aberration were calculated via Zernike vector analysis and used as HOA parameters along with total HOAs. Area under the receiver operating characteristic curve (AUROC) values for each wavefront parameter for pretopographic KC were compared.

Results:
Control eyes and eyes with pretopographic KC had significantly lower ocular or corneal total HOAs and Zernike vector terms than those with clinical KC and topographic KC, except for ocular tetrafoil between topographic KC and pretopographic KC and spherical aberration among all groups. The AUROCs for corneal total HOAs and corneal coma for pretopographic KC and control eyes were 0.781 (100% sensitivity and 47% specificity) and 0.735 (73% sensitivity and 73% specificity), respectively.

Conclusion:
Corneal total HOAs and corneal coma exhibited a potential ability to discriminate pretopographic KC from normal control eyes.
Association between chronic low back pain and regional brain atrophy in a Japanese older population: the Hisayama Study
Authors: Asada Masako , Shibata Mao , Hirabayashi Naoki , Ohara Tomoyuki , Furuta Yoshihiko , Nakazawa Taro , Honda Takanori , Hata Jun , Hosoi Masako , Sudo Nobuyuki , Yamaura Ken , Ninomiya Toshiharu 
Published: March 2022

Abstract
Chronic low back pain (CLBP) is the leading cause of years lived with disability. Recently, it has been reported that CLBP is associated with alterations in the central nervous system. The present study aimed to investigate the association between CLBP and regional brain atrophy in an older Japanese population. A total of 1106 community-dwelling participants aged ≥65 years underwent brain magnetic resonance imaging scans and a health examination in 2017 to 2018. We used the FreeSurfer software for the analysis of brain magnetic resonance imaging. Chronic pain was defined as subjective pain for ≥3 months. Participants were divided into 3 groups according to the presence or absence of chronic pain and the body part that mainly suffered from pain: a “no chronic pain (NCP)” group (n = 541), “CLBP” group (n = 189), and “chronic pain in body parts other than the lower back (OCP)” group (n = 376). The brain volumes of the ventrolateral and dorsolateral prefrontal cortex, the posterior cingulate gyrus, and the amygdala were significantly lower in the CLBP group than in the NCP group after adjustment for sociodemographic, physical, and lifestyle factors and depressive symptoms. In addition, the left superior frontal gyrus was identified as a significant cluster by the Query, Design, Estimate, Contrast interface. There were no significant differences in the brain volumes of pain-related regions between the NCP and the OCP groups. The present study suggests that CLBP is associated with lower brain volumes of pain-related regions in a general older population of Japanese.
Patterns of Enrollment in Cancer Treatment Trials During the COVID-19 Pandemic at National Cancer Institute–Designated Cancer Centers
Authors: Prindiville Sheila A. , Sarosy Gisele A. , Loose David , Ciolino Henry , Doroshow James H. 
Published: March 2022

Abstract
The COVID-19 pandemic posed unprecedented strain on enrollment to cancer clinical trials and their conduct. Here, we highlight an analysis using information from the National Cancer Institute (NCI) Clinical Trials Reporting Program database to describe enrollment patterns to interventional cancer treatment trials at NCI-Designated Cancer Centers during the pandemic. Enrollment to cancer treatment trials at NCI-Designated Cancer Centers decreased precipitously early in the pandemic and has not yet fully returned to the 2019 baseline as of mid-2021. We discuss possible reasons for this and how some of the changes in clinical trial conduct implemented during the pandemic may become part of the standard conduct of NCI-supported clinical trials and broaden access to trials.
Lessons From the Impact of the COVID-19 Pandemic at the National Cancer Institute
Authors: Karzai Fatima , Dahut William L. 
Published: March 2022

Abstract
The COVID-19 (coronavirus disease 2019) pandemic has worldwide implications on health care, especially in our most vulnerable population: cancer patients. Flexibility and adaptation are needed to continue clinical research and for clinical trial development. At the Intramural Research Program, National Cancer Institute, swift changes have been implemented to protect our patients while maintaining the scientific integrity of our cancer clinical trials. Many lessons have been learned including incorporation of telehealth into clinical trials, partnerships with the oncology community at both academic institutions and community practices, focusing on diversity and inclusion to improve scientific innovation, and strengthened relationships with regulatory agencies and institutional review boards. These changes will enhance the clinical trials we conduct well beyond the pandemic.
Clinical Evidence Generation During a Pandemic
Authors: Rivera Donna R. , Kluetz Paul G. , Abdallah Kald , Agrawal Sundeep , Angus Derek C. , Califf Robert M. , Garrett-Mayer Elizabeth , Hyer Randall , Lowy Douglas R. , Khleif Samir N. 
Published: March 2022

Abstract
Because of significant adaptations forced by the COVID-19 pandemic, resultant changes within health care delivery and clinical research introduced the potential for evaluation of novel evidence generation approaches in oncology. On July 26 and 27, 2021, the National Academies of Science, Engineering, and Medicine, National Cancer Policy Forum hosted a virtual workshop entitled “Cancer Care and Cancer Research in the Context of the COVID-19 Pandemic: A Workshop on Lessons Learned.” This workshop examined changes in cancer care and cancer research that occurred in response to the COVID-19 pandemic and considered lessons learned from that experience. The goal was to identify what changes could improve the delivery of high-quality cancer care and the conduct of cancer clinical trials in the postpandemic era, with an emphasis on health equity. How can we sustain the valuable lessons learned that might accelerate progress and enhance clinical evidence generation for patients and clinicians? In this overview, we discuss ways in which the COVID-19 experience has catalyzed research efficiencies as well as fostered a broader array of trial design and research methods that may facilitate improved cancer drug development during the pandemic and beyond.
Outcomes after application of halothoracic orthosis for cervical spine trauma
Authors: Steiner Joel , Kimmel Lara A. , Tomkins Jonathan B. , Wheeler Karly N. , Liew Susan 
Published: March 2022

Background:
Cervical spine fractures can be managed operatively or nonoperatively, considering injury type and patient factors. Nonoperative management may include application of a halothoracic orthosis (HTO). The aim of our study was to describe our patients managed with HTO, review their 6-month and 12-month outcomes, and identify associated factors.

Methods:
Patients fitted with an HTO at our institution in 2014 were included. Data collected included patient demographics, hospital-related data, and radiological union. Injury detail and 6-month and 12-month patient-reported outcomes (Glasgow Outcomes Scale Extended and return to work [RTW]) were accessed through Victorian Orthopedic Trauma Outcomes Registry. Factors related to these outcomes were included in a mixed-effect regression model for each outcome.

Results:
Eighty-six patients (median age 46.5 years) of whom 52 (60%) were male individuals were included. Two-thirds (57 patients) were road trauma patients, and 58 patients (67%) experienced an isolated injury. Thirty-seven patients (43%) experienced a C2 fracture and 27 (31%) experienced a facet fracture. Twelve-month follow-up was completed for 78 patients (91%) with 27 (35%) reporting a good recovery, and 65% (31/48) patients returned to work. Factors associated with lower odds of RTW included compensation, a facet joint fracture, and experiencing comorbidities. No factors were significantly associated with functional outcome, although female individuals exhibited a slower recovery trajectory than male individuals.

Conclusion:
Many patients reported poor 12-month outcomes after HTO for traumatic injury. Factors associated with worse outcomes should be considered when deciding on management of patients with cervical spine fractures.
Correlation between kinesthetic motor imagery of an amputated limb and phantom limb pain
Authors: Yoshimura Manabu , Kurumadani Hiroshi , Hirata Junya , Date Shota , Ueda Akio , Ishii Yosuke , Senoo Katsutoshi , Hanayama Kozo , Sunagawa Toru 
Published: March 2022

Background:
Phantom limb pain (PLP) is a frequent painful sensation in amputees, and motor imagery (MI) is a useful approach for the treatment of this type of pain. However, it is not clear regarding the best MI modality for PLP.

Objectives:
The purpose of this study was to investigate the relationship between the PLP and MI modality in upper limb amputees.

Study design:
Observational study.

Methods:
Eleven patients who underwent unilateral upper limb amputation participated in this study. The MI modality (kinesthetic and visual) and PLP intensity were evaluated using the Kinesthetic and Visual Imagery Questionnaire (KVIQ)-20 and a visual analog scale. MI ability was also assessed during the hand mental rotation task. We examined the correlation between MI modalities, ability, and pain intensity.

Results:
The total KVIQ kinesthetic score was negatively correlated with pain intensity (r = −0.71, P < 0.01): the more vivid the kinesthetic imagery, the weaker the pain. In particular, the reduction in pain intensity was associated with strong kinesthetic imagery of opposing movements of the deficient thumb (r = −0.81, P < 0.01). The KVIQ visual score and MI ability were not associated with pain intensity.

Conclusions:
Our data showed that the reduction of PLP could be associated with the kinesthetic modality of MI but not with visual modality or MI ability. In other words, it was suggested that the more vivid the sensation of moving muscles and joints in the defect area, the lower the PLP intensity. To reduce PLP, clinicians may prefer interventions using the kinesthetic modality.
Polypharmacy Is Associated With Falls in Women With and Without HIV
Authors: Psomas Christina K. , Hoover Donald R. , Shi Qiuhu , Brown Todd T. , Vance David E. , Holman Susan , Plankey Michael W. , Tien Phyllis C. , Weber Kathleen M. , Floris-Moore Michelle , Bolivar Hector H. , Golub Elizabeth T. , McDonnell Holstad Marcia , Radtke Kendra K. , Tamraz Bani , Erlandson Kristine M. , Rubin Leah H. , Sharma Anjali 
Published: March 2022

Background:
Aging in people with HIV is associated with increased risk of developing synergistic conditions such as neurocognitive impairment, polypharmacy, and falls. We assessed associations between polypharmacy (use of 5 or more non-ART medications), use of neurocognitive adverse effects (NCAE) medications, and odds of falls in women with HIV (WWH) and without HIV (HIV−).

Methods:
Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH and 557 HIV-) Women's Interagency HIV Study participants between 2014 and 2016. Polypharmacy and NCAE medication use were evaluated separately and jointly in multivariable models to assess their independent contributions to single and multiple falls risk.

Results:
The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51% vs. 41%; P < 0.001) and NCAE medication use (44% vs. 37%; P = 0.01) than HIV- women. Polypharmacy conferred elevated odds of single fall [adjusted odds ratio (aOR) 1.67, 95% CI: 1.36 to 2.06; P < 0.001] and multiple falls (aOR 2.31, 95% CI: 1.83 to 2.93; P < 0.001); the results for NCAE medications and falls were similar. Both polypharmacy and number of NCAE medications remained strongly and independently associated with falls in multivariable models adjusted for HIV serostatus, study site, sociodemographics, clinical characteristics, and substance use.

Conclusions:
Polypharmacy and NCAE medication use were greater among WWH compared with HIV-, and both were independently and incrementally related to falls. Deprescribing and avoidance of medications with NCAEs may be an important consideration for reducing fall risk among WWH and sociodemographically similar women without HIV.
Thiosulfatihalobacter marinus gen. nov. sp. nov., a novel member of the family Roseobacteraceae, isolated from the West Pacific Ocean
Authors: Wu Yuehong , Ren Wen-Ting , Zhong Ying-Wen , Guo Li-Li , Zhou Peng , Xu Xue-Wei 
Published: March 2022

Two strains (GL-11-2T and ZH2-Y79) were isolated from the seawater collected from the West Pacific Ocean and the East China Sea, respectively. Cells were Gram-stain-negative, strictly aerobic, non-motile and rod-shaped. Cells grew in the medium containing 0.5–7.5 % NaCl (w/v, optimum, 1.0–3.0 %), at pH 6.0–8.0 (optimum, pH 6.5–7.0) and at 4–40 °C (optimum, 30 °C). H2S production occurred in marine broth supplemented with sodium thiosulphate. The almost-complete 16S rRNA gene sequences of the two isolates were identical, and exhibited the highest similarity to

Pseudoruegeria aquimaris

JCM 13603T (97.5 %), followed by

Ruegeria conchae

TW15T (97.2%),

Shimia aestuarii

DSM 15283T (97.1 %) and

Ruegeria lacuscaerulensis

ITI-1157T (97.0 %). Phylogenetic analysis revealed that the isolates were affiliated with the family

Roseobacteraceae

and represented an independent lineage. The sole isoprenoid quinone was ubiquinone 10. The principal fatty acids were summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and cyclo-C19 : 0
ω8c. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and diphosphatidylglycerol. The DNA G+C content was 62.3 mol%. The orthologous average nucleotide identity, in silico DNA–DNA hybridization and average amino acid identity values among the genomes of strain GL-11-2T and the reference strains were 73.2–79.0, 20.3–22.5 and 66.0–80.8 %, respectively. Strains GL-11-2ᵀ and ZH2-Y79 possessed complete metabolic pathways for thiosulphate oxidation, dissimilatory nitrate reduction and denitrification. Phylogenetic distinctiveness, chemotaxonomic differences and phenotypic properties revealed that the isolates represent a novel genus and species of the family

Roseobacteraceae

, belonging to the class

Alphaproteobacteria

, for which the name Thiosulfatihalobacter marinus gen. nov., sp. nov. (type strain, GL-11–2T=KCTC 82723T=MCCC M20691T) is proposed.
The contribution of white matter pathology, hypoperfusion, lesion load, and stroke recurrence to language deficits following acute subcortical left hemisphere stroke
Authors: Sharif Massoud S. , Goldberg Emily B. , Walker Alexandra , Hillis Argye E. , Meier Erin L. 
Published: March 2022

AbstractAphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. Compared to subcortical stroke patients without aphasia, patients with aphasia had greater acute and total lesion volume, were older, and had significantly greater damage to the internal capsule (which did not survive controlling for total lesion volume). Patients with aphasia did not differ from non-aphasic patients by other demographic or stroke variables. Age was the only significant predictor of aphasia status in a logistic regression model. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals.
Pin1-promoted SUMOylation of RNF168 restrains its chromatin accumulation
Authors: Chauhan Anoop Singh , Garvin Alexander J. , Jamshad Mohammed , Morris Joanna R. 
Published: March 2022

AbstractThe E3 ubiquitin ligase RNF168 is a rate-limiting component of DNA double-strand break signalling that acts to amplify histone ubiquitylation. The confining of RNF168 chromatin spreading around DNA break sites has been related to constraining its expression levels and to the removal of ubiquitin-conjugates to which it binds. Here we identify a new mechanism that suppresses RNF168 amplification at chromatin. We show that depletion of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) or mutation of the Pin1-binding site of RNF168 increases DNA-damage site accumulation of RNF168 to supraphysiological levels without impacting RNF168 expression levels. Pin1 promotes SUMOylation of RNF168 by SUMO2/3, and a SUMO conjugation site on RNF168 is required to restrict RNF168 accumulations. We find Pin1-SUMO mediated-regulation of RNF168 is associated with cellular radioresistance. These data demonstrate that the regulation of chromatin ubiquitylation is actively suppressed by modification of RNF168 to counteract excessive RNF168-ubiquitin spreading.
Hyperactive immature state and differential CXCR2 expression of neutrophils in severe COVID-19
Authors: Rice Christopher M. , Lewis Philip , Ponce-Garcia Fernando M. , Gibbs Willem , Cela Drinalda , Hamilton Fergus , Arnold David , Hyams Catherine , Oliver Elizabeth , Barr Rachael , Goenka Anu , Davidson Andrew , Wooldridge Linda , Finn Adam , Rivino Laura , Amulic Borko 
Published: March 2022

AbstractNeutrophils are vital in defence against pathogens but excessive neutrophil activity can lead to tissue damage and promote acute respiratory distress syndrome (ARDS). COVID-19 is associated with systemic expansion of immature neutrophils but the functional consequences of this shift to immaturity are not understood. We used flow cytometry to investigate activity and phenotypic diversity of circulating neutrophils in acute and convalescent COVID-19 patients. First, we demonstrate hyperactivation of immature CD10−subpopulations in severe disease, with elevated markers of secondary granule release. Partially activated immature neutrophils were detectable three months post symptom onset, indication long term myeloid dysregulation in convalescent COVID-19 patients. Second, we demonstrate that neutrophils from moderately ill patients downregulate the chemokine receptor CXCR2, while neutrophils from severely ill individuals failed to do so, suggesting altered ability for organ trafficking and a potential mechanism for induction of disease tolerance. CD10−and CXCR2hineutrophil subpopulations were enriched in severe disease and may represent prognostic biomarkers for identification of individuals at high risk of progressing to severe COVID-19.
A weakly structured stem for human origins in Africa
Authors: Ragsdale Aaron P. , Weaver Timothy D. , Atkinson Elizabeth G. , Hoal Eileen , Möller Marlo , Henn Brenna M. , Gravel Simon 
Published: March 2022

AbstractWhile it is now broadly accepted that Homo sapiens originated within Africa, considerable uncertainty surrounds specific models of divergence and migration across the continent. Progress is hampered by a paucity of fossil and genomic data, as well as variability in prior divergence time estimates. Here we use linkage disequilibrium and diversity-based statistics, optimized for rapid, complex demographic inference to discriminate among such models. We infer detailed demographic models for populations across Africa, including representatives from eastern and western groups, as well as 44 newly whole-genome sequenced individuals from the Nama (Khoe-San). Despite the complexity of African population history, contemporary population structure dates back to Marine Isotope Stage (MIS) 5. The earliest population divergence among contemporary populations occurs 120-135ka, between the Khoe-San and other groups. Prior to the divergence of contemporary African groups, we infer long-lasting structure between two or more weakly differentiated ancestral Homo populations connected by gene flow over hundreds of thousands of years (i.e. a weakly structured stem). We find that weakly structured stem models provide more likely explanations of polymorphism that had previously been attributed to contributions from archaic hominins in Africa. In contrast to models with archaic introgression, we predict that fossil remains from coexisting ancestral populations should be morphologically similar. Despite genetic similarity between these populations, an inferred 1–4% of genetic differentiation among contemporary human populations can be attributed to genetic drift between stem populations. We show that model misspecification explains variation in previous divergence time estimates and argue that studying a suite of models is key to robust inferences about deep history.