bluuebunny/crossref_metadata_2025 huggingface dataset:
Third trimester uterine artery Doppler for prediction of adverse perinatal outcomes
Authors: Duncan Jose R. , Schenone Claudio V. , Običan Sarah G.
Published: July 2022

Purpose of review

Abnormal uterine artery Doppler (UtAD) studies early in gestation have been associated with adverse pregnancy outcomes. However, their association with complications in the third trimester is weak. We aim to review the prediction ability for perinatal complications of these indices in the third trimester.

Recent findings

Abnormal UtAD waveforms in the third trimester are associated with preeclampsia, small-for-gestational age infants (SGA), preterm birth, perinatal death, and other perinatal complications, such as cesarean section for fetal distress, 5 min low Apgar score, low umbilical artery pH, and neonatal admission to the ICU, particularly in SGA infants. UtAD prediction performance is improved by the addition of maternal characteristics as well as biochemical markers to prediction models and is more precise if the evaluation is made closer to delivery or diagnosis.

This review shows that the prediction accuracy of UtAD for adverse pregnancy outcomes during the third trimester is moderate at best. UtAD have limited additive value to prediction models that include PlGF and sFlt-1. Serial assessments rather than a single third trimester evaluation may enhance the prediction performance of the UtAD combined models.
Nonsurgical management of adenomyosis: an overview of current evidence
Authors: Lazaridis Alexandros , Grammatis Alexandros L. , Spencer Stuart , Hirsch Martin
Published: July 2022

Purpose of review

Adenomyosis is a condition where endometrium-like tissue spreads within the myometrium. Although its prevalence in the general population is not exactly known, its clinical manifestations are well established and include pelvic pain, dysmenorrhea (painful periods), heavy menstrual bleeding and subfertility [1]. Adenomyosis often coexists with other gynaecological conditions, such as endometriosis or fibroids, and may cloud the clinical presentation [2]. The aim of this article is to review current noninterventional, nonsurgical management modalities and wherever possible offer information that allows women to make safe and informed choices regarding their treatment options.

Recent findings

Recent studies support that medical strategies, including the Mirena coil, Dienogest and GnRH antagonists, are efficient in improving adenomyosis-associated symptoms. High-quality evidence is scarce and is needed to properly counsel women with this condition. Future research should prioritize overall pain, menstrual bleeding, quality of life and live birth as primary outcomes and assess women with different grades of adenomyosis.

This review provides the most current evidence with regards to the nonsurgical management of adenomyosis. In light of the paucity and low quality of existing data, high-quality trials are needed to definitely determine the impact of conservative and medical treatment on the clinical management of adenomyosis.
Long-term Growth, Functional, and Aesthetic Outcomes after Fibula Free Flap Reconstruction for Mandibulectomy Performed in Children
Authors: Shahzad Farooq , Henderson Peter W. , Matros Evan , Cordeiro Peter G.
Published: July 2022

Background:

The long-term outcome of mandible reconstruction when performed in children has not been well documented.

Methods:

This is a retrospective case series of patients who underwent immediate oncologic mandible reconstruction with a fibula free flap at younger than 18 years of age over a 20-year period, by a single surgeon, who had long-term follow-up.

Results:

A total of 10 patients met inclusion criteria. Patient age ranged from 3 years and 8 months to 17 years and 9 months (mean 11 years). The etiology was malignant tumors in seven patients and benign locally aggressive tumors in three patients. All fibula flaps survived. All donor sites were closed primarily. The mean follow-up duration was 10 years and 5 months (range 3–20 years). The mean patient age at follow-up was 21 years and 10 months (range 8 years and 9 months to 30 years and 9 months). All patients achieved a regular diet and normal speech. Final occlusion was normal in seven of 10 patients. The aesthetic outcome, as evaluated by clinical examination, was a symmetric mandible in eight patients (in the other two the aesthetic asymmetry and malocclusion was minor and did not require operative intervention). Dental implants were ultimately placed in three patients. Leg function was normal in eight patients. Achilles lengthening and tendon transfer was required in one patient, and one patient developed ankle pain associated with running.

Conclusion:

Mandible reconstruction in children with the fibula free flap provides excellent aesthetic and functional outcomes that are durable over time.
Updates on Coronavirus Disease 2019 in Children in Japan
Authors: Aizawa Yuta , Takanashi Sayaka , Ogimi Chikara
Published: July 2022

This review provides updates on coronavirus disease 2019 (COVID-19) in children in Japan by summarizing published data. By the end of March 2022, Japan had experienced 6 waves of COVID-19 outbreaks. Over this time, the clinical features presented among children have changed in the context of the predominant variants. Although the COVID-19 pandemic affected children in terms of medical, physical and psychosocial aspects, the clinical outcomes have been favorable in Japan compared with those in some European countries and the United States, which may be partly due to a lower incidence of multisystem inflammatory syndromes in children and obesity. The COVID-19 vaccine has been available for children; however, the vaccination rate in children 5–11 years of age is lower than that in older children due to the government’s lack of an active approach in this specific population. Further action is needed to improve the overall vaccination rates in children.
Pasteurella multocida as a Rare Cause of Neonatal Meningitis Complicated by Empyema
Authors: Norlin Casey , Courtney Ashleah , Evers Michael , Reeves Ashley , Gauthreaux Courtney , Romito Joseph , Hescock George
Published: July 2022

A neonatal male injured by the family dog developed meningitis secondary to Pasteurella multocida. After initially defervescing with IV antibiotic treatment, he became febrile again, and imaging revealed a skull fracture and fluid collection. Following neurosurgical evacuation and an extended course of antibiotics, the patient was discharged home.
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.
Chronic Diarrhea Associated with Edwardsiella Tarda Gastroenteritis: A Case Report and Literature Review
Authors: Chida Rie , Iio Kazuki , Kaizuka Haruki , Hirai Yuji , Ishida Yu , Yamanaka Gaku
Published: July 2022

Edwardsiella tarda, a Gram-negative bacterium classified into the genus Enterobacteriaceae, causes self-limited gastroenteritis. Here, we report a case of E. tarda gastroenteritis in a previously healthy 12-year-old boy in whom inflammatory bowel disease was precluded by endoscopy and tissue biopsy due to 3-month history of diarrhea, abdominal pain and weight loss.
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.
Multifocal Infantile Hepatic Hemangiomas Complicated by Consumptive Hypothyroidism: The Benefits of Early Diagnosis and Treatment
Authors: Morais Catarina Granjo , Alves Inês , Coelho Janine , Vilares Ana Teresa , Do Bom-Sucesso Maria
Published: July 2022

Infantile hepatic hemangiomas (IHH) account for 12% of all childhood hepatic tumors. Most IHH are diagnosed within the first 6 months of life and involute spontaneously; however, some require medical treatment. The present report describes a case of multifocal IHH associated with subcutaneous and lingual hemangiomas, complicated by consumptive hypothyroidism and successfully managed with oral propranolol and thyroid replacement therapy, without documented adverse effects. Consumptive hypothyroidism is a rare complication of IHH, but suggestive of multifocal/diffuse subtypes. The authors intend to reinforce the importance of early referral to a Vascular Anomalies Center and treatment with propranolol in selected patients.
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

Background

Population-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.

Methods

We 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.

Results

We 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.

Conclusions

Caregiver 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

WDR62 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

Background

A 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.

Methods

This 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.

Results

The 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.

Conclusions

These 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.

summary

Spike-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

Ancient, 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

Visual 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.
The activation of ATR during unperturbed DNA replication is restricted by VCP/p97 through the extraction of DNA polymerase α/Primase from chromatin
Authors: Rodríguez-Acebes Sara , Martín-Rufo Rodrigo , Gómez-Moya Alicia , Churcher Scott B , Fernández-Llorente Alejandro , de la Vega-Barranco Guillermo , Perona Alejandra , Oroz Pilar , Martín-Doncel Elena , Toledo Luis Ignacio , Méndez Juan , Lecona Emilio
Published: July 2022

The replication stress response is an essential pathway that deals with the obstacles that halt the progression of DNA replication forks even during an unperturbed S phase. Basal activation of the ATR and CHK1 kinases prevents the premature firing of origins of replication during S phase, avoiding the activation of an excessive number of replication forks and the appearance of genomic instability. However, the mechanisms that regulate ATR activation in the unperturbed S phase have not been fully determined. Here we present evidence that the AAA ATPase VCP/p97 regulates the presence of the DNA polymerase α/Primase complex (POLA/PRIM) on chromatin, thus limiting its activity and hampering the subsequent activation of ATR by TOPBP1. As a consequence, inhibiting VCP/p97 activates ATR and CHK1 and leads to a cell cycle arrest in G2/M. We propose that the priming activity of POLA/PRIM in the lagging strand is one of the determinants of the basal activation of ATR during an unperturbed S phase and VCP/p97 limits this activation through the extraction of POLA/PRIM from chromatin.
The response mechanism of oreorchis patens (Lindl.) Lindl. to cold stress
Authors: Yu Lan , Xu Yufeng , Zhang Yuyan , Shao Meini , Miao Qing , Chen Xuhui , Yang Huixia , Cui Na , Qu Bo
Published: July 2022

Cold stress, a major environmental factor, has an important impact on the production of landscape plants and crop yield, and its stress and resistance mechanisms have always been hot research issues. Oreorchis patens (Lindl.) Lindl., an important germplasm resource, has strong frost resistance and can resist low temperatures of -40 °C. However, the mechanism by which O. patens responds to cold stress remains poorly understood. Here, we examined the adaptation to the low-temperature environment of O. patens by changing the leaf tissue structure, while the synergistic effect of osmotic regulation, reactive oxygen scavenging and protein improved the resistance to cold stress. In addition, analysis of the photosynthetic system showed that cold stress changes the photosynthetic capacity of O. patens leaves to affect cold resistance. Analysis by nonparametric transcriptome sequencing revealed 2402 genes that were differentially expressed, most of which were related to resistance. Simultaneously, quantitative real-time polymerase chain reaction (qRT-PCR) analysis obtained results consistent with the transcriptome. These results indicated that O. patens could alter leaf structure and physiological and biochemical metabolic processes by initiating resistance-related molecular regulatory networks to improve the ability to resist cold stress. This study was the first to discuss the physiological, biochemical and molecular regulatory mechanisms of O. patens resistance to cold stress, which laid a foundation for revealing the biological and molecular mechanisms of overwintering of O. patens and breeding cold-resistant horticultural crops in northern China.
TM-Vec: template modeling vectors for fast homology detection and alignment
Authors: Hamamsy Tymor , Morton James T. , Berenberg Daniel , Carriero Nicholas , Gligorijevic Vladimir , Blackwell Robert , Strauss Charlie E. M. , Leman Julia Koehler , Cho Kyunghyun , Bonneau Richard
Published: July 2022

Exploiting sequence-structure-function relationships in molecular biology and computational modeling relies on detecting proteins with high sequence similarities. However, the most commonly used sequence alignment-based methods, such as BLAST, frequently fail on proteins with low sequence similarity to previously annotated proteins. We developed a deep learning method, TM-Vec, that uses sequence alignments to learn structural features that can then be used to search for structure-structure similarities in large sequence databases. We train TM-Vec to accurately predict TM-scores as a metric of structural similarity for pairs of structures directly from sequence pairs without the need for intermediate computation or solution of structures. For remote homologs (sequence similarity ≤ 10%) that are highly structurally similar (TM-score ? 0.6), we predict TM-scores within 0.026 of their value computed by TM-align. TM-Vec outperforms traditional sequence alignment methods and performs similar to structure-based alignment methods. TM-Vec was trained on the CATH and SwissModel structural databases and it has been tested on carefully curated structure-structure alignment databases that were designed specifically to test very remote homology detection methods. It scales sub-linearly for search against large protein databases and is well suited for discovering remotely homologous proteins.
Perfect genetic biomarkers for cancer from a fresh view of gene dysregulation
Authors: Gil Gabriel , Gonzalez Augusto
Published: July 2022

Over the last decades, a host of gene expression profiles of tumor and normal tissue samples have been recorded by many microarray and RNA-Seq projects. Much of this big data awaits a full understanding and exploitation for translational cancer research. In particular, the pressing need to discover gene panels for diagnosis and therapy have not received yet a definitive answer. Here, we tackle such a question through rigorous mining of some of the currently available data. Our mining scheme rests on formal concept analysis and rough set theory and allows us to identify perfect gene panels for twelve of the solid tumors reported in the TCGA database. We dub them ‘perfect gene panels’ because they perfectly discriminate between normal and tumor samples. To wit, testing the gene expression profiles against a tumor or normal pattern provides no false positive and no false negative cases (i.e., 100% sensitivity and 100% specificity). Hence, perfect gene panels might be useful genetic markers for cancer diagnosis. Furthermore, we stress that such panels come in many flavors depending on the gene expression levels we choose as a pattern to check. For instance, there are perfect panels where a single gene over-expression signals a tumor and others where a single non-silenced gene is an indication of a tumor-free sample, just to mention two out of eight possible cases. Remarkably, some panels also suggest suitable genetic targets for therapeutic interventions, since they define normal samples by tuning the expression level of a single gene.
Prior parental experience attenuates hormonal stress responses and alters hippocampal glucocorticoid receptors in both sexes of the biparental rock dove
Authors: Farrar Victoria S. , Gallardo Jaime Morales , Calisi Rebecca M.
Published: July 2022

In the face of challenges, animals must balance investments in reproductive effort versus their own survival. Physiologically, this tradeoff may be mediated by glucocorticoid release by the hypothalamic-pituitary-adrenal (HPA) axis and prolactin release from the pituitary to maintain parental care. The degree to which animals react to, and recover from, stressors likely affects their ability to maintain parental behavior and ultimately, fitness. However, less is known about how the stress response changes when animals gain parental experience, and what mechanisms may underlie any effect of experience on hormonal stress responses. To address these questions, we measured the corticosterone (CORT) and prolactin (PRL) stress response in both sexes of the biparental rock dove (Columba livia) that had never raised chicks versus birds that had fledged at least one chick. We measured both CORT and PRL at baseline and after an acute stressor (30 minutes restraint). We also measured negative feedback ability by administering dexamethasone, a synthetic glucocorticoid that suppresses CORT release, and measuring CORT and PRL after 60 minutes. All hormones we measured when birds were not actively nesting, allowing us to assess any lasting effects of parental experience beyond the parental care period. Birds with parental experience had lower stress-induced and negative-feedback CORT, and higher stress-induced PRL than inexperienced birds. In a separate experiment, we measured glucocorticoid receptor subtype expression in the hippocampus, a key site of negative feedback regulation. We found that experienced birds expressed higher glucocorticoid receptors than inexperienced controls, which may mediate their ability to attenuate the hormonal stress response. Together, these results shed light on potential mechanisms by which gaining experience may improve parental performance and fitness.

Summary statement

Experienced rock dove parents show lower corticosterone and higher prolactin levels after an acute stressor than birds without parental experience and increased glucocorticoid receptor expression in the hippocampus may mediate this effect.
Characterization of Mechanics Driven Heterogeneity in Mesenchymal Stromal Cells
Authors: Kaonis Samantha , Aboellail Zack , Ghosh Soham
Published: July 2022

Mesenchymal stromal or stem cells (MSC) are one of the most promising candidates for a myriad of cell therapy applications because of their multipotency, trophic properties and immunomodulatory properties. Despite showing promises in numerous preclinical and clinical studies, MSC based therapy is not yet a reality for regenerative medicine due their suboptimal outcome at the clinical endpoint. Suboptimal function of MSC is often attributed to the monolayer expansion process on plastic which is a necessary condition to reach the therapeutically relevant number, and also to their response to a fibrotic environment post transplantation. In both scenarios of plastic culture and fibrotic conditions, the mechanical environment experienced by the MSC is completely different from the natural mechanical niche of the MSC. Accordingly, the role of mechanical environment has been shown to be a critical determinant of MSC gene expression and function. In this study we report that human bone marrow derived primary MSC population becomes phenotypically heterogenous when they experience an abnormal mechanical environment, compared to their native environment. Using a newly developed technique to quantify the heterogeneity, we provide the evidence of phenotypical heterogeneity of MSC through high resolution imaging and image analysis. Additionally, we provide mechanistic insight of the origin of such substrate mechanics driven heterogeneity, which is further determined by the cell-cell mechanical communication through the substrate. The outcome of this study might provide mechanism driven design principles to the molecular, cellular and tissue engineering researchers for rational design of MSC culture condition and biomaterials, thus improving their functional outcome.
Characterization of DNA processing protein A (DprA) of the radiation-resistant bacterium Deinococcus radiodurans
Authors: Sharma Dhirendra Kumar , Misra Hari S. , Rajpurohit Yogendra S.
Published: July 2022

The uptake of environmental DNA (eDNA) by certain bacteria and its integration into their genome creates genetic diversity and new phenotypes. A DNA processing protein A (DprA) is part of a multiprotein complex and facilitate natural transformation (NT) phenotype in most bacteria. The Deinococcus radiodurans, an extremely radioresistant bacterium, is efficient in N T, and its genome encodes nearly all the components of the natural competence complex. Here, we have characterized the DprA of this bacterium (DrDprA) for the known characteristics of DprA proteins in other bacteria and the mechanisms underlying its roles in the transformation of eDNA into the bacterial genome. DrDprA is found to be a unique domain organization implicating some unique functions compared with DprA of other bacteria. In vitro studies showed that the purified recombinant DrDprA binds to both ssDNA and dsDNA with nearly equal affinity and protects ssDNA from nucleolytic degradation. DrDprA showed a strong interaction with DrRecA indicating its role in RecA catalyzed functions in vivo. Mutational studies identified amino acid residues responsible for its oligomerization, interaction with DrRecA, and DNA binding characteristics of DrDprA. Further, we demonstrated that both oligomerization and DNA binding properties of DrDprA are integral to its support in DrRecA catalyzed strand exchange reaction (SER) in vitro. These results suggested that DrDprA is largely structurally conserved with DprA homologs but showed some unique structure-function features like additional domain, the same affinity to ss/ds DNA and both oligomerization and DNA binding domains collectively contribute to its support in DrRecA functions.
Characterization of rumen microbiome and metabolome from an oro-esophageal probe and fluid, particulate and fluid-particulate fractions from rumen fistula in Holstein dairy cows
Authors: da Cunha Lais L. , Monteiro Hugo F. , Canisso Igor F. , Bicalho Rodrigo C. , Cardoso Felipe C. , Weimer Bart C. , Lima Fabio S.
Published: July 2022

Less invasive rumen sampling methods such as oro-esophageal probes became widely popular to explore the rumen microbiome and metabolome. However, it remains unclear if such methods represent well the rumen contents from fluid and particulate fractions. Herein, we characterized the microbiome and metabolome in rumen content collected by an oro-esophageal probe and fluid, particulate, and the combined fluid-particulate fractions collected by rumen fistula in ten multiparous Holstein dairy cows. The 16S rRNA gene was amplified and sequenced using the Illumina MiSeq platform. Untargeted metabolome was characterized using gas chromatography of a time-of-flight mass spectrometer. Although the pH of oro-esophageal samples was greater than those of fluid, fluid-particulate, and particulate ones, we found no difference in alpha and beta-diversity of their microbiomes. Bacteroidetes, Firmicutes, and Proteobacteria were consistently the top three most abundant phyla representing ~90% of all detected phyla across all samples. The overall metabolome PLS-DA of oro-esophageal samples was similar to the fluid-particulate samples but differed from fluid and particulate. Enrichment analysis pathways revealed few differences between oro-esophageal and fluid-particulate samples, such as the synthesis of unsaturated fatty acids. The results of the current study suggest that oro-esophageal sampling can be a proxy to screen the rumen microbiome with the 16S platform and overall fluid-particulate metabolome for a single-time and diet context. Nonetheless, studies focusing specifically on fluid and particulate metabolomes and specific metabolic pathways should carefully consider the sampling method used.

IMPORTANCE

The techniques used to collect the rumen contents (oro-esophageal probe and rumen fistula) suggested potential differences in the populations of rumen microbes, and the implications of these techniques for high throughput studies characterizing the rumen microbiome and metabolome need further elucidation. Ten rumen-fistulated Holstein dairy cows were used to characterize the microbiome and metabolome of samples collected using an oro-esophageal probe and the rumen-fistula fluid, particulate, and fluid-particulate fractions. The results of the current study suggest that oro-esophageal sampling represents well the rumen microbiome and overall fluid-particulate metabolome. However, fluid and particulate metabolomes and specific metabolic pathways across all types of rumen samples differed, indicating that studies focused on the characterization of rumen metabolome variable fractions should carefully consider the sampling method used.