bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal Cross-resistance to Tenofovir in Children and Adolescents Failing ART Makes Them Eligible for Tenofovir-Lamivudine-Dolutegravir Treatment
Authors: Steegen Kim , Levin Leon , Evans Denise , Technau Karl-Günter , Hans Lucia 
Published: July 2022

Background:
Fixed-dose combination of dolutegravir (DTG) with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) likely improves adherence and has a favorable resistance profile. We evaluated predicted efficacy of TLD (TDF-3TC-DTG) in children and adolescents failing abacavir (ABC), zidovudine (AZT), or TDF containing regimens.

Methods:
Drug resistance mutations were analyzed in a retrospective dataset of individuals <19 years of age, failing ABC (n = 293) AZT (n = 288) or TDF (n = 69) based treatment. Pol sequences were submitted to Stanford HIVdb v8.9. Genotypic susceptibility scores were calculated for various DTG-containing regimens.

Results:
Genotypes were assessed for 650 individuals with a median age of 14 years (IQR 10-17 years). More individuals failed a protease inhibitor (PI)-based (78.3%) than a non-nucleoside reverse transcriptase inhibitors (NNRTI)-based (21.7%) regimen. Most individuals in the AZT group (n = 288; 94.4%) failed a PI-based regimen, compared with 71.0% and 64.2% in the TDF (n = 69) and ABC group (n = 293). Genotypic sensitivity scores <2 to TLD were observed in 8.5% and 9.4% of ABC- and AZT-exposed individuals, compared with 23.2% in the TDF group. The M184V mutation was most often detected in the ABC group (70.6%) versus 60.0% and 52.4% in TDF and AZT groups. The presence of K65R was rare (n = 13, 2.0%) and reduced TLD susceptibility was commonly caused by accumulation of nucleoside reverse transcriptase inhibitor (NRTI) mutations.

Conclusions:
Cross-resistance to TDF was limited, further reducing concerns about use of transition to TLD in children and adolescents. The NADIA trial has subsequently shown that patients failing a TDF/3TC/EFV regimen can safely be transitioned to a TLD regimen but we do not have data for patients failing an ABC/3TC/NNRTI or PI regimens. Frequent virological monitoring is recommended after switch to DTG, especially in children continuing ABC in the backbone. Clinical studies correlating predicted resistance with clinical outcomes, especially in settings without access to genotyping, are required.
Placebo effect in the treatment of non-small cell lung cancer: a meta-analysis
Authors: Ren Siyuan , Ma Mengyao , He Chuan , Deng Yuhui , Chen Xiaoyun , Liu Yonglin , Jin Yangyang , Liu Yansong , Cai Lei , He Lin 
Published: July 2022

Objective:
The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined.

Methods:
PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models.

Results:
Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], -0.126-0.609) and dropout rate of 2.1% (95% CrI, 0.007-0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017-0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76-0.96) for the achievement of progression-free survival and overall survival, respectively.

Conclusion:
In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.
The Association Between Continuity of Care With a Primary Care Physician and Duration of Work Disability for Low Back Pain
Authors: Sheehan Luke R. , Di Donato Michael , Gray Shannon E. , Lane Tyler J. , van Vreden Caryn , Collie Alex 
Published: July 2022

Objectives
The aims of the study are to determine the continuity of care (CoC) provided by primary care physicians among workers with low back pain, to identify factors associated with CoC, and to investigate whether CoC is associated with working time loss.

Methods
Continuity of care was measured with the usual provider continuity metric. Ordinal logistic regression models examined factors associated with CoC. Quantile regression models examined the association between working time loss and CoC.

Results
Complete CoC was observed in 33.8% of workers, high CoC among 37.7%, moderate CoC in 22.1%, and low CoC in 6.4%. In workers with more than 2-months time loss, those with complete CoC had less time off work.

Conclusions
Higher CoC with a primary care physician is associated with less working time loss and this relationship is strongest in the subacute phase of low back pain.
The association between helicopter emergency medical services and early casualty survival: a nationwide study
Authors: Guinzburg Ariel , Gelikas Shaul , Tsur Avishai M. , Nadler Roy , Sorkin Alex , Avital Guy , Radomislensky Irina , Bodas Moran , Segal David , Benov Avi , Chen Jacob 
Published: July 2022

Background
Helicopter emergency medical services (HEMS) allow for shorter transport duration in long-distance evacuations and facilitate advanced en-route medical care access. Studies comparing HEMS with ground emergency medical services (GEMS), including the outcome of prehospital mortality, are lacking.

Objective
This study aimed to evaluate the association between HEMS and early mortality in Israel.

Setting
A retrospective cohort study was conducted of the cross-referenced Israel Defense Forces Trauma Registry and Israel National Trauma Registry databases.

Outcome measures and analysis
Univariable logistic regression was used to assess the association between HEMS and early mortality, defined as mortality within 1 day of the injury. Regression analysis was further performed stratifying by event type (military or civilian) or type of injury (penetrating or nonpenetrating).

Results
A total of 2344 casualties were included in the study, of whom 756 (32.3%) were evacuated by air. Early mortality rates were 90/1588 (5.7%) and 37/756 (4.9%) in GEMS and HEMS groups, respectively. Regression analysis found no significant analysis between HEMS and early mortality [OR, 0.86 (95% CI, 0.57–1.26)]. Stratified by event type, a nonsignificant association between HEMS and early mortality was demonstrated for combat [OR, 1.69 (95% CI, 0.79–3.92)] and noncombat [OR, 0.73 (95% CI, 0.4–1.25)] events. HEMS was associated with decreased early mortality among casualties with a penetrating injury [OR, 0.59 (95% CI, 0.34–0.98)] but not associated with early mortality among casualties with a nonpenetrating injury [OR, 0.84 (95% CI, 0.43–1.52)].

Conclusion
HEMS was not associated with a decrease in early mortality among trauma casualties in this study encompassing the prehospital and hospital scenes. There was a positive trend and a decrease in mortality from penetrating injuries. Further research to ascertain which casualties benefit from HEMS is warranted and will allow for more precise use of this expensive resource.
Assessing Physician Resident Contributions to Outpatient Clinical Workload
Authors: Kashner T. Michael , Greenberg Paul B. , Henley Steven S. , Bowman Marjorie A. , Sanders Karen M. 
Published: July 2022

Background:
Graduate medical education is centered in hospitals despite a care system where patients mostly receive their care in an outpatient setting. Such gaps may exist because of inadequate funding for residency positions in community and hospital-based clinics.

Objective:
Determine if physician residents’ contribution to outpatient workload offsets their costs for supervision, salary, and fringe benefits as residents acquire skills to become independent practitioners.

Research Design:
VA’s electronic patient records from 2005 through 2018 were analyzed using generalized linear mixed models to estimate resident and staff contributions to workload in relative value units.

Measures:
Resident participation rate is resident contributed workload net of supervision as a percent of total clinic workload. Productivity is per diem resident workload as a percent of per diem staff workload. Efficiency is per dollar resident workload as a percent of per dollar staff workload. Progressive independence is annual rate of change in resident productivity.

Results:
Average participation rates varied by specialty from 6% to 22%, with 11% (primary care) and 13% (psychiatry). Productivity rates ranged from 21% to 94%, with 57% (primary care) and 61% (psychiatry). Efficiency rates varied from 0.63 to 3.81, with 1.69 (primary care), 1.89 (psychiatry). Progressive independence rates varied from 2.7%/year (psychiatry) to 39.7%/year (specialty care).

Conclusions:
Although residents rotating through most VA clinics generate revenue to cover their direct costs as they learn, some federal subsidies may be necessary to encourage hospital- and community-based clinics to accept residents from the less profitable primary care and mental health specialties.
American Society of Plastic Surgeons Evidence-Based Clinical Practice Guideline: Eyelid Surgery for Upper Visual Field Improvement
Authors: Kim Kenneth K. , Granick Mark S. , Baum Gregory A. , Beninger Francis , Cahill Kenneth V. , Donnelly Katelyn C. , Kaidi Ashton A. , Kang Ajaipal S. , Loeding Lauren , Loyo Myriam , Patel Parit A. , Roostaeian Jason , Taghva Goretti Ho , Varkarakis George M. 
Published: July 2022

Background:
A group of experts from different disciplines was convened to develop guidelines for the management of upper visual field impairments related to eyelid ptosis and dermatochalasis. The goal was to provide evidence-based recommendations to improve patient care.

Methods:
A multidisciplinary group of experts representing their specialty organizations was selected. A systematic literature review was performed including topics regarding documentation of the underlying cause for visual field impairment, selection of an appropriate surgical repair, assessment of the type of anesthesia, the use of adjunctive brow procedures, and follow-up assessments. The Grading of Recommendations, Assessment, Development, and Evaluation methodology process was used to evaluate the relevant studies. Clinical practice recommendations were developed using BRIDGE-Wiz (Building Recommendations In a Developers’ Guideline Editor) software.

Results:
Each topic area was assessed. A clinical recommendation was made, and the relevant literature was discussed.

Conclusions:
The review of the literature revealed varied complication rates and diverse treatment modalities for the correction of upper visual field deficit. Strong recommendations could not be made in most topic areas because of a paucity of methodologically sound studies in the literature. More rigorously designed studies are needed to measure outcomes of interest, with fewer sources of potential error or bias.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Anterior Synostotic Plagiocephaly: A Quantitative Analysis of Craniofacial Features Using Computed Tomography
Authors: Mohan Nivana , Lazarus Lelika , Harrichandparsad Rohen , Madaree Anil 
Published: July 2022

The premature fusion of one coronal suture causes anterior synostotic plagiocephaly (ASP), which results in overt craniofacial dysmorphology that could be challenging to correct. This study aimed to document and compare the morphometry of the anterior cranial fossa (ACF), orbit, and ear on the ipsilateral (synostotic) and contralateral (nonsynostotic) sides in a select cohort of South African patients with ASP, using computed tomography (CT) scans. The dimensions of the ACF, orbit and the position of the ear on the ipsilateral and contralateral sides were measured using a set of anatomical landmarks on 2-dimensional CT scans of 18 consecutive patients diagnosed with nonsyndromic ASP. The differences between the ipsilateral and contralateral sides were calculated and expressed as a percentage of the contralateral side. All ACF parameters decreased significantly on the ipsilateral side when compared to the contralateral side, resulting in the volume of the ACF being the most affected (−27.7%). In terms of the orbit, on the ipsilateral side, the length-infraorbital rim, height, and surface area parameters increased significantly, with the height being the most affected (24.6%). The remaining orbital parameters (length-supraorbital rim, breadth and volume) decreased significantly, with the length-supraorbital rim parameter being the most affected (−10.8%). The ipsilateral ear was found to be displaced anteriorly (9.33 mm) and caudally (5.87 mm) from the contralateral ear. These measures may be useful to surgeons during corrective surgery by indicating the degree of the asymmetry on each side, making it easier to plan the technique and extent of surgical correction of the affected structures.
Acculturative orientations among Hispanic/Latinx caregivers in the ABCD Study: Associations with caregiver and youth mental health and youth brain function
Authors: Meca Alan , Peraza Julio A. , Riedel Michael C. , Hale Willie , Pettit Jeremy W. , Musser Erica D. , Salo Taylor , Flannery Jessica S. , Bottenhorn Katherine L. , Dick Anthony S. , Lobo Rosario Pintos , Ucros Laura M. , Greaves Chelsea A. , Hawes Samuel W. , Sanchez Mariana , Gonzalez Marybel R. , Sutherland Matthew T. , Gonzalez Raul , Laird Angela R. 
Published: July 2022

ABSTRACTBackgroundPopulation-based neuroscience offers opportunities to examine important but understudied sociocultural factors, such as acculturation. Acculturation refers to the extent to which an individual retains their cultural heritage and / or adopts the receiving society’s culture and is particularly salient among Hispanic/Latinx immigrants. Specific acculturative orientations have been linked to vulnerability to substance use, depression, and suicide and are known to influence family dynamics between caregivers and their children.MethodsWe investigated first- and second-generation Hispanic/Latinx caregivers in the ABCD Study and examined how caregivers’ acculturative orientation impacts their mental health, as well as the mental health of their children. In addition, we evaluated how caregiver orientation is associated with adolescent socio-affiliative neural function in the ventromedial prefrontal cortex, insula, and temporoparietal junction.ResultsWe identified two caregiver acculturation profiles: bicultural (retains heritage culture while adopting US culture) and detached (discards heritage culture and rejects US culture). Bicultural caregivers exhibited fewer symptoms of depression, avoidant behaviors, and inattention compared to detached caregivers; further, youth exhibited similar internalizing effects across caregiver profiles. Moreover, youth with bicultural caregivers displayed increased resting-state brain activity in the left insula; however, differences in long-range functional connectivity were not significant.ConclusionsCaregiver acculturation is an important familial-environmental factor in Hispanic/Latinx families linked to significant differences in caregiver and youth mental health and youth insula activity. Future work should examine sociocultural and neurodevelopmental changes across adolescence to assess health outcomes and determine whether localized, corticolimbic brain effects are ultimately translated into long-range connectivity differences.
Microcephaly-associated WDR62 mutations hamper Golgi apparatus-to-spindle pole shuttling in human neural progenitors
Authors: Dell’Amico Claudia , Angulo Salavarria Marilyn M. , Takeo Yutaka , Saotome Ichiko , Dell’Anno Maria Teresa , Galimberti Maura , Pellegrino Enrica , Cattaneo Elena , Louvi Angeliki , Onorati Marco 
Published: July 2022

AbstractWDR62 is a spindle pole-associated scaffold protein with pleiotropic functions during corticogenesis. Recessive mutations in WDR62 are associated with structural brain abnormalities and account for the second most common cause of autosomal recessive primary microcephaly (MCPH), indicating WDR62 as a critical hub for human brain development. Here, we investigated a C-terminal truncating mutation (D955AfsX112) in WDR62 using induced pluripotent stem cells (iPSCs) obtained from a patient with MCPH2. We generated neuroepithelial stem (NES) cells and cerebro-cortical progenitors and neurons from patient-derived and isogenic retro-mutated iPSC lines. We found that WDR62 dysfunction resulted in impaired cell cycle progression and alterations of the neurogenic trajectories of iPSC neuroderivatives. Moreover, we report WDR62 localization at the Golgi apparatus during interphase, both in human neural progenitors in vitro and in human fetal brain tissue. WDR62 shuttling from the Golgi apparatus to spindle poles is dynamic and microtubule-dependent. Impairment of WDR62 function and localization results in severe neurodevelopmental abnormalities, thus delineating new mechanisms in MCPH etiology.
Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication
Authors: Tani Naoki , Ikematsu Hideyuki , Goto Takeyuki , Gondo Kei , Inoue Takeru , Yanagihara Yuki , Kurata Yasuo , Oishi Ryo , Minami Junya , Onozawa Kyoko , Nagano Sukehisa , Kuwano Hiroyuki , Akashi Koichi , Shimono Nobuyuki , Chong Yong 
Published: July 2022

AbstractBackgroundA SARS-CoV-2 mRNA vaccine booster elicits sufficient antibody responses that protect against COVID-19, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use.MethodsThis is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 two-dose primary series. Spike-specific IgG titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for seven days following vaccination through a web-based self-reporting diary.ResultsThe data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (beta=0.305, p<0.001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk: 3.97 [95% confidence interval: 2.48-6.35]); however, the IgG titers after the booster dose were not affected by fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication.ConclusionsThese results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions would not interfere with the elevation of specific IgG titers.summarySpike-specific IgG titers after a BNT162b2 booster were measured for healthcare workers. Adverse reactions and self-medicated antipyretics were reported. Post-booster vaccination fever was correlated with the specific IgG titers. Antipyretics used for adverse reactions did not suppress specific IgG induction.
Hidden species diversity in a living fossil vertebrate
Authors: Brownstein Chase D. , Kim Daemin , Orr Oliver D. , Hogue Gabriela M. , Tracy Bryn H. , Pugh M. Worth , Singer Randal , Myles-McBurney Chelsea , Mollish Jon Michael , Simmons Jeffrey W. , David Solomon R. , Watkins-Colwell Gregory , Hoffman Eva A. , Near Thomas J. 
Published: July 2022

SummaryAncient, species-poor lineages persistently occur across the Tree of Life. These evolutionarily unique lineages are likely to contain unrecognized species diversity masked by the low rates of morphological evolution that characterize living fossils [1, 2]. Halecomorphi is a major clade of ray-finned fishes that diverged from its closest relatives over 200 million years ago [3, 4] yet is represented by only one recognized living species in eastern North America, the Bowfin Amia calva Linnaeus. Here, we use double digest restriction-site associated DNA (ddRAD) sequencing and high-resolution computed tomography to illuminate recent speciation in the bowfins. Our results support the resurrection of a second living species of Bowfin with the timing of diversification dating to the Pleistocene. In turn, we expand the species diversity of an ancient lineage that is integral to studies of vertebrate genomics and development [2, 3, 5], yet is facing growing conservation threats driven by the caviar fishery [6].
Temporal gradient characteristics of automatic neural representation for orthographic consistency in Chinese characters
Authors: Liu Jianyi , Fan Tengwen , Chen Yan , Zhao Jingjing 
Published: July 2022

AbstractVisual word processing involves the automatic decoding of orthographic, phonological and semantic information. The mappings of these information in a writing system comprise an important feature of visual words: orthographic regularity and consistency. Recent electroencephalography (EEG) studies have investigated the automatic processing mechanism of orthographic regularity (i.e., words vs. pseudowords) among visual words. However, the automated mechanism and temporal dynamics of different types of orthographic consistency effects (e.g., orthographic positional consistency, orthography-to-phonology consistency vs. orthography-to-semantics consistency) have never been studied. This study explored automatic neural representation for orthographic consistency effects in visual words and its temporal dynamics through an oddball paradigm. Three types of oddball sequences were designed with Chinese characters as stimuli, including consistent Chinese characters as standard stimuli and three types of inconsistent characters (orthographic positional inconsistent, orthography-to-phonology inconsistent vs. orthography-to-semantics inconsistent) as deviant stimuli, respectively. Significant visual mismatch negativity (vMMN) activities were observed in all three types of inconsistent characters, which suggests automatic processing caused by orthographic consistency violations. Time-resolved representational similarity analysis (RSA) further revealed that there are different temporal dynamics of automatic neural representations for the three types of consistency features. The representation of positional consistency emerged earlier within an independent time window, while the representation of phonetic and semantic consistency emerged later, and partially overlapped. These findings provide novel insights for the temporal gradient characteristics of automated representation structure of orthography consistency information.