bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection Analysis Identifies Clusters of Unusual Mutational Changes in Omicron Lineage BA.1 That Likely Impact Spike Function
Authors: Martin Darren P. , Lytras Spyros , Lucaci Alexander G. , Maier Wolfgang , Grüning Björn , Shank Stephen D. , Weaver Steven , MacLean Oscar A. , Orton Richard J. , Lemey Philippe , Boni Maciej F. , Tegally Houriiyah , Harkins Gordon W. , Scheepers Cathrine , Bhiman Jinal N. , Everatt Josie , Amoako Daniel G. , San James Emmanuel , Giandhari Jennifer , Sigal Alex , Williamson Carolyn , Hsiao Nei-yuan , von Gottberg Anne , De Klerk Arne , Shafer Robert W. , Robertson David L. , Wilkinson Robert J. , Sewell B. Trevor , Lessells Richard , Nekrutenko Anton , Greaney Allison J. , Starr Tyler N. , Bloom Jesse D. , Murrell Ben , Wilkinson Eduan , Gupta Ravindra K. , de Oliveira Tulio , Kosakovsky Pond Sergei L.
Published: March 2022

Among the 30 nonsynonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (1) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (2) interactions of Spike with ACE2 receptors, and (3) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any virus within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and, in combination with other mutations, adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron overall previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
Vitamin D concentrations during pregnancy and in cord blood: a systematic review and meta-analysis
Authors: Wong Rosa S , Tung Keith T S , Mak Ray T W , Leung Wing Cheong , Yam Jason C , Chua Gilbert T , Fung Genevieve P G , Ho Macro H K , Wong Ian C K , Ip Patrick
Published: March 2022

Context

Effect size estimates for the association between vitamin D concentrations in maternal blood during pregnancy and in cord blood vary widely across studies, but no meta-analysis has been conducted to ascertain this association.

Objective

The aim of this systematic review was to estimate the pooled effect size for the association between circulating 25-hydroxyvitamin D (25[OH]D) concentrations, a marker of vitamin D status, in maternal blood during pregnancy and in cord blood.

Data Sources

The PubMed, Embase, and Web of Science databases were searched from their inception to February 2021.

Data Extraction

Following the application of prespecified inclusion and exclusion criteria, 94 articles were eligible for full-text review, which was conducted by 2 authors independently. A third author was consulted when necessary and consensus reached. In total, 26 articles, which comprised 30 studies and 6212 mother-infant dyads, were included. Methodological quality was assessed using a modified version of the Joanna Briggs Institute’s Critical Appraisal Checklist for Studies Reporting Prevalence Data. Correlation coefficient (r) values for the association between maternal serum 25(OH)D concentrations during pregnancy and in cord blood were extracted.

Data Analysis

The r values were pooled using random-effects meta-analyses. Sensitivity and subgroup analyses were performed to investigate sources of heterogeneity. The pooled r for all studies was 0.72 (95%CI, 0.64–0.79), indicating high heterogeneity (I2 = 95%, P < 0.01). After influential and outlier studies were removed, the pooled r for 9 studies was 0.70 (95%CI, 0.66–0.74), which resulted in a substantial reduction in heterogeneity (I2 = 41%, P=0.10).

Conclusion

The findings support a positive and large correlation between maternal vitamin D concentrations during pregnancy and vitamin D concentrations in cord blood.

Systematic Review Registration

PROSPERO registration number CRD42021273348.
Suzaku observations of Fe K-shell lines in the supernova remnant W 51 C and hard X-ray sources in the proximity
Authors: Shimaguchi Aika , Nobukawa Kumiko K , Yamauchi Shigeo , Nobukawa Masayoshi , Fujita Yutaka
Published: March 2022

In this paper, we investigate the Fe K-shell lines in the supernova remnant W 51 C and hard X-ray sources in the proximity. We measure the intensities of the Fe i Kα and Fe xxv Heα lines at 6.40 and 6.68 keV, respectively, and find that the intensity of the 6.68 keV line is consistent with the background level expected from previous studies, while that of the 6.40 keV line is higher at the significance level of 2.0σ. Given the presence of gamma-ray emission and high ionization rate point spatially coincident with the remnant, we conclude that the enhanced 6.40 keV line most likely originates from the interaction between low-energy cosmic rays and molecular clouds. Also, we discover an enhanced 6.68 keV line emission from the compact H ii region G49.0−0.3 at a significance level of 3.4σ. Spectral analysis reveals that the temperature and abundance of the thermal plasma with the 6.68 keV line is $kT=3.0^{+0.8}_{-0.7}$ keV and Z = 0.5 ± 0.2 solar, respectively. These values are explained by the thermal plasma generated by the stellar winds of O stars.
Trimeric photosystem I facilitates energy transfer from phycobilisomes in Synechocystis sp. PCC 6803
Authors: Akhtar Parveen , Biswas Avratanu , Balog-Vig Fanny , Domonkos Ildikó , Kovács László , Lambrev Petar H
Published: March 2022

In cyanobacteria, phycobilisomes (PBS) serve as peripheral light-harvesting complexes of the two photosystems, extending their antenna size and the wavelength range of photons available for photosynthesis. The abundance of PBS, the number of phycobiliproteins they contain, and their light-harvesting function are dynamically adjusted in response to the physiological conditions. PBS are also thought to be involved in state transitions that maintain the excitation balance between the two photosystems. Unlike its eukaryotic counterpart, PSI is trimeric in many cyanobacterial species and the physiological significance of this is not well understood. Here, we compared the composition and light-harvesting function of PBS in cells of Synechocystis sp. PCC 6803, which has primarily trimeric PSI, and the ΔpsaL mutant, which lacks the PsaL subunit of PSI and is unable to form trimers. We also investigated a mutant additionally lacking the PsaJ and PsaF subunits of PSI. Both strains with monomeric PSI accumulated significantly more allophycocyanin per chlorophyll, indicating higher abundance of PBS. On the other hand, a higher phycocyanin:allophycocyanin ratio in the wild type suggests larger PBS or the presence of APC-less PBS (CpcL-type) that are not assembled in cells with monomeric PSI. Steady-state and time-resolved fluorescence spectroscopy at room temperature and 77 K revealed that PSII receives more energy from the PBS at the expense of PSI in cells with monomeric PSI, regardless of the presence of PsaF. Taken together, these results show that the oligomeric state of PSI impacts the excitation energy flow in Synechocystis.
MAP KINASE PHOSPHATASE1 promotes osmotolerance by suppressing PHYTOALEXIN DEFICIENT4-independent immunity
Authors: Uchida Kohei , Yamaguchi Masahiro , Kanamori Kazuki , Ariga Hirotaka , Isono Kazuho , Kajino Takuma , Tanaka Keisuke , Saijo Yusuke , Yotsui Izumi , Sakata Yoichi , Taji Teruaki
Published: March 2022

Initial exposure of plants to osmotic stress caused by drought, cold, or salinity leads to acclimation, termed acquired tolerance, to subsequent severe stresses. Acquired osmotolerance induced by salt stress is widespread across Arabidopsis (Arabidopsis thaliana) accessions and is conferred by disruption of a nucleotide-binding leucine-rich repeat gene, designated ACQUIRED OSMOTOLERANCE. De-repression of this gene under osmotic stress causes detrimental autoimmunity via ENHANCED DISEASE SUSCEPTIBILITY1 and PHYTOALEXIN DEFICIENT4 (PAD4). However, the mechanism underlying acquired osmotolerance remains poorly understood. Here, we isolated an acquired osmotolerance-defective mutant (aod13) by screening 30,000 seedlings of an ion beam-mutagenized M2 population of Bu-5, an accession with acquired osmotolerance. We found that AOD13 encodes the dual-specificity phosphatase MAP KINASE PHOSPHATASE1 (MKP1), which negatively regulates MITOGEN-ACTIVATED PROTEIN KINASE3/6 (MPK3/6). Consistently, MPK3/6 activation was greater in aod13 than in the Bu-5 wild-type (WT). The aod13 mutant was sensitive to osmotic stress but tolerant to salt stress. Under osmotic stress, pathogenesis-related genes were strongly induced in aod13 but not in the Bu-5 WT. Loss of PAD4 in pad4 aod13 plants did not restore acquired osmotolerance, implying that activation of immunity independent of PAD4 renders aod13 sensitive to osmotic stress. These findings suggest that AOD13 (i.e. MKP1) promotes osmotolerance by suppressing the PAD4-independent immune response activated by MPK3/6.
Primary Care Physical Therapists’ Experiences When Screening for Serious Pathologies Among Their Patients: A Qualitative Study
Authors: Budtz Cecilie Rud , Rønn-Smidt Helle , Thomsen Janus Nikolaj Laust , Hansen Rikke Pilegaard , Christiansen David Høyrup
Published: March 2022

Objective

A vital part of the initial examination performed by a physical therapist is to establish whether the patient would benefit from physical therapist intervention. This process includes knowledge about contraindications for treatment and screening for serious pathologies. However, little is known about the physical therapists' views and thoughts about their own practice when screening for serious pathologies. The purpose of this study was to explore the experience gained by physical therapists when screening for serious pathologies among their patients.

Methods

This was a qualitative study based on individual semi-structured interviews with 9 primary care physical therapists. The interviews were analyzed using reflexive thematic analysis, and generated themes were explained and reported with relevant quotes.

Results

Three overall themes were generated: (1) the role of physical therapists in the diagnostic process; (2) responsibility from the individual to the group; and (3) the difficult task of cooperation. The physical therapists described how they relied more on their clinical suspicion than on asking red-flag questions when screening for serious pathologies. They also questioned their differential diagnostic abilities. Finally, they saw a potential to further enhance their confidence in the area by reflecting on the matter with colleagues and by receiving more feedback about their clinical reasoning regarding serious pathologies from general practitioners.

Conclusion

These findings suggest that physical therapists primarily rely on their clinical suspicion when screening for serious pathologies but at the same time are uncertain about their differential diagnostic abilities.

Impact

These findings can inform future interventions targeting the physical therapists' abilities to detect serious pathology.
Using patient-reported data from a smartphone app to capture and characterize real-time patient-reported flares in rheumatoid arthritis
Authors: Gandrup Julie , Selby David A , van der Veer Sabine N , Mcbeth John , Dixon William G
Published: March 2022

Objective

We aimed to explore the frequency of self-reported flares and their association with preceding symptoms collected through a smartphone app by people with RA.

Methods

We used data from the Remote Monitoring of RA study, in which patients tracked their daily symptoms and weekly flares on an app. We summarized the number of self-reported flare weeks. For each week preceding a flare question, we calculated three summary features for daily symptoms: mean, variability and slope. Mixed effects logistic regression models quantified associations between flare weeks and symptom summary features. Pain was used as an example symptom for multivariate modelling.

Results

Twenty patients tracked their symptoms for a median of 81 days (interquartile range 80, 82). Fifteen of 20 participants reported at least one flare week, adding up to 54 flare weeks out of 198 participant weeks in total. Univariate mixed effects models showed that higher mean and steeper upward slopes in symptom scores in the week preceding the flare increased the likelihood of flare occurrence, but the association with variability was less strong. Multivariate modelling showed that for pain, mean scores and variability were associated with higher odds of flare, with odds ratios 1.83 (95% CI, 1.15, 2.97) and 3.12 (95% CI, 1.07, 9.13), respectively.

Conclusion

Our study suggests that patient-reported flares are common and are associated with higher daily RA symptom scores in the preceding week. Enabling patients to collect daily symptom data on their smartphones might, ultimately, facilitate prediction and more timely management of imminent flares.
DOSIMETRY IN DIGITAL BREAST TOMOSYNTHESIS: COST-EFFICIENT APPROACH FOR THE SOUTH AMERICAN PERSPECTIVES
Authors: Pirchio Rosana , Pérez Gonzalo Nicolás , Ratto Santiago Scinardo , Stefanic Amalia María
Published: March 2022

The measurement of air kerma in air (Kair) to estimate average glandular dose (AGD) received during digital breast tomosynthesis (DBT) studies is sometimes a difficult task. In this work, a novel methodology was implemented to measure Kair and half-value layer while the X-ray tube is rotating. A low economic cost support (LCS) was built to place aluminium sheets and a calibrated dosemeter. Three Fujifilm Innovality equipment were used and two dosemeters calibrated on W–Al energies. Validation of the new methodology was made against standard scheme and it was applied to estimate AGD for 300 patients and 7 phantoms. Validation analysis was satisfactory. The difference in the AGD calculated with the LCS and DICOM Header was lower than ±10%. AGD values ranged from 0.77 to 2.11 mGy and 0.85 to 2.15 mGy for phantoms and patients, respectively. The novel methodology has a potential use for DBT equipment without stationary mode.
Predicting stress and depressive symptoms using high-resolution smartphone data and sleep behavior in Danish adults
Authors: Otte Andersen Thea , Skovlund Dissing Agnete , Rosenbek Severinsen Elin , Kryger Jensen Andreas , Thanh Pham Vi , Varga Tibor V , Hulvej Rod Naja
Published: March 2022

Study Objectives

The early detection of mental disorders is crucial. Patterns of smartphone behavior have been suggested to predict mental disorders. The aim of this study was to develop and compare prediction models using a novel combination of smartphone and sleep behavior to predict early indicators of mental health problems, specifically high perceived stress and depressive symptoms.

Methods

The data material included two separate population samples nested within the SmartSleep Study. Prediction models were trained using information from 4522 Danish adults and tested in an independent test set comprising of 1885 adults. The prediction models utilized comprehensive information on subjective smartphone behavior, objective night-time smartphone behavior, and self-reported sleep behavior. Receiver operating characteristics area-under-the-curve (ROC AUC) values obtained in the test set were recorded as the performance metrics for each prediction model.

Results

Neither subjective nor objective smartphone behavior was found to add additional predictive information compared to basic sociodemographic factors when forecasting perceived stress or depressive symptoms. Instead, the best performance for predicting poor mental health was found in the sleep prediction model (AUC = 0.75, 95% CI: 0.72–0.78) for perceived stress and (AUC = 0.83, 95%CI: 0.80–0.85) for depressive symptoms, which included self-reported information on sleep quantity, sleep quality and the use of sleep medication.

Conclusions

Sleep behavior is an important predictor when forecasting mental health symptoms and it outperforms novel approaches using objective and subjective smartphone behavior.
‘They didnae tell you nothin’: The Failings of Sex Education, Antenatal Care, and Welfare Bureaucracies in Glasgow, c. 1970s–2000s
Authors: Greenlees Janet
Published: March 2022

Utilizing group oral histories from nineteen women who were pregnant and living in areas of social and economic deprivation in Glasgow, Scotland, between the late 1970s and early 2000s, this article analyses the difficulties the women faced in accessing information about pregnancy and welfare entitlements. It reveals a disconnect between women’s knowledge about reproduction and maternal health and welfare benefits and the political initiatives designed to improve antenatal care and pregnancy outcomes in Britain since the 1980 Short Report. This divide was widened by a broader Scottish culture of reticence around sex education and the ongoing moral influence of the churches. The article clarifies the class-blind English arguments within the patient consumer model that was promoted since the 1960s. It demonstrates how marginal groups were ill equipped to participate as patient consumers, either individually or as a collective group. More broadly, this article gives voice to an underrepresented group and highlights how these women utilized adaptive decision-making to navigate their pregnancy journeys in a society with uneven maternity and welfare provision and inhibitions about sex education. By highlighting the realities of marginality and lived experiences, it adds nuance to conventional welfare and policy histories.
Maize Anthracnose Stalk Rot in the Genomic Era
Authors: Belisário Renata , Robertson Alison E. , Vaillancourt Lisa J.
Published: March 2022

Anthracnose stalk rot (ASR) of maize results in millions of dollars in losses annually in the United States. ASR, together with anthracnose leaf blight and anthracnose top dieback, is caused by the fungus Colletotrichum graminicola. Current ASR management recommendations emphasize host resistance and reduction of plant stressors (e.g., drought, heat, low fertility, or soil acidity). Stress reduction may be more difficult to achieve in the future due to more high-intensity production protocols and climate change. Moreover, cultural and chemical management practices may conflict with other important goals, including environmental sustainability and maximization of yield potential. Thus, future ASR management may rely more heavily on host resistance, for which there are relatively few highly effective sources. The last comprehensive review of C. graminicola and maize anthracnose was written over two decades ago. The genomic age has brought important new insights into mechanisms governing the host–pathogen interaction from the application of molecular and cytological technologies. This review provides a summary of our current model of maize anthracnose etiology, including how increased knowledge of molecular and cellular events could contribute to better ASR management. Improved understanding of C. graminicola taxonomy has confirmed that the fungus is specific to Zea mays, and that it colonizes living maize tissues via a critical biotrophic phase. Successful biotrophic establishment relies on an array of secreted protein effectors and secondary metabolites produced at different stages of infection and dispersed to multiple locations. These molecules could provide therapeutic targets for the next generation of transgenic or gene-edited ASR-resistant hybrids.
Rice Stripe Virus Modulates the Feeding Preference of Small Brown Planthopper from the Stems to Leaves of Rice Plants to Promote Virus Infection
Authors: Guo Wei , Du Linlin , Li Chenyang , Ma Shuhui , Wang Zhaoyun , Lan Ying , Lin Feng , Zhou Yijun , Wang Yunyue , Zhou Tong
Published: March 2022

Research on plant–virus–vector interactions has revealed that viruses can enhance their spread to new host plants by attracting nonviruliferous vectors to infected plants or driving viruliferous vectors to noninfected plants. However, whether viruses can also modulate the feeding preference of viruliferous vectors for different plant parts remains largely unknown. Here, by using rice stripe virus (RSV) and its vector, the small brown planthopper (SBPH), as a model, the effect of the virus on the feeding preference of its vector was studied by calculating the number of nonviruliferous and viruliferous SBPHs settling on different parts of rice plants. The results showed that the RSV-free SBPHs significantly preferred feeding on the stems of rice plants, whereas RSV-carrying SBPHs fed more on rice leaves. Moreover, the rice plants inoculated with RSV on the leaves showed more severe symptoms, with enhanced disease incidence and virus accumulation compared with rice plants inoculated at the top and bottom of stems, suggesting that the leaves are more susceptible to RSV than the stems of rice plants. These results demonstrate that RSV modulates the feeding preference of its transmitting vector SBPH from the stems to leaves of rice plants to promote virus infection. Interestingly, we also found that the leaves were more susceptible than the stems to rice black-streaked dwarf virus. This study proves that the feeding preference of insect vectors can be modulated by plant viruses to facilitate virus transmission.
The History of Surgical Education in the United States: Past, Present, and Future
Authors: Camison Liliana , Brooker Jack E. , Naran Sanjay , Potts John R. , Losee Joseph E.
Published: March 2022

In just over 100 years, surgical education in the United States has evolved from a disorganized practice to a refined system esteemed worldwide as one of the premier models for the training of physicians and surgeons. But in the changing environment of health care, new challenges have arisen that could warrant a reform. To design our future, we must understand our past. The present work is not intended to be a comprehensive account of the history of American surgery. Instead, it tells the abridged history of surgical education in our country: the evolution from apprenticeships to residencies; the birth of hospital-based teaching; the impact of key historical events on training; the marks left by some preeminent characters; the conception of regulatory entities that steer our education; and, finally, how our process of training surgeons might need to be refined for the continued progress of our profession. Told in chronological order in a manner that will be memorable to readers, this story weaves together the key events that explain how our current surgical training models came to be. We conclude with a timely invitation to draw from these past lessons to redesign the future of graduate medical education, making a case for the transition to time-variable, competency-based medical education for surgical residency programs in America.
Nursing Faculty Informatics Competencies
Authors: Bove Lisa Anne , Sauer Penny
Published: March 2022

It is essential that nurses can use technology and accurately record and interpret clinical data to deliver efficient and effective patient care. The purpose of this study was to determine the level of nursing faculty informatics competencies and to learn about barriers faculty find in teaching informatics. Using a cross-sectional design, faculty were surveyed about their knowledge and comfort in teaching informatics using the Self-Assessment of Informatics Competency Scale for Health Professionals instrument. The aggregate mean (SD) score of the Self-Assessment of Informatics Competency Scale for Health Professionals basic knowledge and skills competency subscale and role subscale were was 3.36 (0.437) and 3.35 (0.711), respectively, which showed overall proficiency with these competencies. The aggregate mean (SD) for the applied computer skills competency was 2.25 (0.842), which showed less proficiency in higher-level informatics skills. Reported barriers to integrating informatics into courses were technology issues (17.2%), lack of knowledge (15.5%), and a lack of resources (12.1%). Some faculty reported that the concept of informatics was confusing (3.5%) and students were not engaged in the concepts (3.5%). Faculty with informatics competence can help students advance the use of technology and informatics at the bedside to improve patient care.
Incisional Biopsy Technique Is Associated With Decreased Overall Survival for Cutaneous Melanoma
Authors: Liszewski Walter , Stewart Jacob R. , Vidal Nahid Y. , Demer Addison M.
Published: March 2022

BACKGROUND

Previous studies examining melanoma biopsy technique have not demonstrated an effect on overall survival.

OBJECTIVE

To examine overall survival of patients with cutaneous melanoma diagnosed by shave, punch, incisional, or excisional techniques from the National Cancer Database (NCDB).

MATERIALS AND METHODS

Melanoma data from the 2004 to 2016 NCDB data set were analyzed. A Cox proportional hazards model was constructed to assess the risk of 5-year all-cause mortality.

RESULTS

In total, 42,272 cases of melanoma were reviewed, with 27,899 (66%) diagnosed by shave biopsy, 8,823 (20.9%) by punch biopsy, and 5,550 (13.1%) by incisional biopsy. Both the univariate and multivariate analyses demonstrated that tumors diagnosed by incisional biopsy had significantly (p = .001) lower overall 5-year survival compared with shave techniques (hazard ratio [HR] = 1.140, 95% confidence interval [CI] 1.055 to 1.231). We found no difference (p = .109) between shave and punch biopsy techniques (HR 1.062, 95% CI 0.987–1.142) or between punch and incisional techniques (HR 1.074, 95% CI 0.979–1.177, p = .131).

CONCLUSION

Incisional biopsies were associated with decreased overall 5-year survival in the NCDB. No difference was observed between shave and punch biopsy techniques. These findings support current melanoma management guidelines.
Recurrence Rate for Melanoma Excised by Mohs Micrographic Surgery Without Immunostaining
Authors: Vieira Carlos , Jennings Tara , Renzi Michael A. , Lawrence Naomi , Decker Ashley
Published: March 2022

BACKGROUND

Mohs micrographic surgery (MMS) is becoming increasingly popular for the treatment of cutaneous melanoma (CM) as multiple studies have demonstrated favorable outcomes for local recurrence and overall survival.

OBJECTIVE

To analyze the outcomes of noninvasive (NIM) and invasive melanomas (IM) using MMS with fresh frozen sections. The primary outcome was local recurrence. The secondary outcome was to identify mean surgical margins based on tumor type and location.

METHODS

Retrospective cohort study of 224 cases of CM treated from 2006 to 2016 at a tertiary academic center with MMS and fresh frozen sections by a single Mohs surgeon.

RESULTS

The overall recurrence rate was 2.6% with a mean follow-up of 36.2 months. The recurrence rate for NIM versus IM was 1.6% and 7%, respectively. The mean margins for NIM and IM were 7.9 mm and 10.1 mm, respectively. These varied by tumor site and location.

CONCLUSION

This study supports the use of MMS in the treatment of CM and highlights how narrower surgical margins for NIM of the head and neck can be achieved without increasing risk of local recurrence.
Processing of pain by the developing brain: evidence of differences between adolescent and adult females
Authors: Tong Han , Maloney Thomas C. , Payne Michael F. , King Christopher D. , Ting Tracy V. , Kashikar-Zuck Susmita , Coghill Robert C. , López-Solà Marina
Published: March 2022

Adolescence is a sensitive period for both brain development and the emergence of chronic pain particularly in females. However, the brain mechanisms supporting pain perception during adolescence remain unclear. This study compares perceptual and brain responses to pain in female adolescents and adults to characterize pain processing in the developing brain. Thirty adolescent (ages 13-17 years) and 30 adult (ages 35-55 years) females underwent a functional magnetic resonance imaging scan involving acute pain. Participants received 12 ten-second noxious pressure stimuli that were applied to the left thumbnail at 2.5 and 4 kg/cm2, and rated pain intensity and unpleasantness on a visual analogue scale. We found a significant group-by-stimulus intensity interaction on pain ratings. Compared with adults, adolescents reported greater pain intensity and unpleasantness in response to 2.5 kg/cm2 but not 4 kg/cm2. Adolescents showed greater medial–lateral prefrontal cortex and supramarginal gyrus activation in response to 2.5 kg/cm2 and greater medial prefrontal cortex and rostral anterior cingulate responses to 4 kg/cm2. Adolescents showed greater pain-evoked responses in the neurologic pain signature and greater activation in the default mode and ventral attention networks. Also, the amygdala and associated regions played a stronger role in predicting pain intensity in adolescents, and activity in default mode and ventral attention regions more strongly mediated the relationship between stimulus intensity and pain ratings. This study provides first evidence of greater low-pain sensitivity and pain-evoked brain responses in female adolescents (vs adult women) in regions important for nociceptive, affective, and cognitive processing, which may be associated with differences in peripheral nociception.
Prenatally Diagnosed Lymphatic Malformations of the Head and Neck
Authors: Wang Nancy , Harris Jacqueline E. , Durand Rachelle , Le Leannec Isabelle C. , Vu Lan , Frieden Ilona J. , Rosbe Kristina W. , Czechowicz Josephine A.
Published: March 2022

Objectives:

To describe prenatal diagnosis and perinatal management of patients with head and neck lymphatic malformations (LMs) at a tertiary fetal diagnostic and vascular anomalies center. To identify prenatal characteristics correlating with the need for airway intervention at birth. To describe postnatal clinical course in patients with prenatally diagnosed head and neck LMs.

Methods:

A retrospective review of all patients with head and neck LMs diagnosed in utero at a tertiary prenatal diagnostic center from 1996 to 2020 was performed. Prenatal records of pregnant patients and postnatal records of patients were reviewed. Univariate and multivariate logistic regression analyses were conducted to identify correlates of need for extrauterine intrapartum treatment (EXIT) delivery and correlates of clinical outcomes.

Results:

Over the study period, 26 fetuses were diagnosed with LM of the head and neck, 15 of which survived the perinatal period. Outcomes in these survivors are reported including birth modality, DeSerres’ stage, duration and modality of treatment, complications, hospitalizations, and functional outcomes including need for tracheostomy and gastrostomy tube. The majority of patients (n = 8) were born via the EXIT modality. Almost half (n = 7) were DeSerres’ stage V. Prenatal imaging findings of neck vessel compression (p = 0.023) and tracheal deviation (p = 0.006) correlated with EXIT delivery. The most common treatment modalities were sclerotherapy (n = 14), surgery (n = 7), and sirolimus (n = 8).

Conclusions:

This study identified prenatal anatomic findings of tracheal deviation and neck vessel compression as factors associated with EXIT delivery. None of the patients in our series required tracheostomy during the EXIT procedure, although 20% eventually underwent tracheostomy. The majority of infants with prenatally diagnosed head and LMs required multimodality treatment with some combination of sclerotherapy, surgery, and medical management, as well as multidisciplinary care from our vascular anomalies team throughout the first years of life and beyond.
Survey of Adult Patients With Vascular Anomalies Reveals Acute Need of Adult Hematologists-Oncologists to Enter the Field
Authors: Iacobas Ionela , Singh Mallika , Finger Mellenee , Klepper Lisa K. , Blei Francine
Published: March 2022

Background:

We have observed that adult patients with vascular anomalies often have limited access to specialists with expertise in vascular anomalies who can coordinate their care and prescribe medications, but evidence-supported statistics needed for advocacy efforts was not available.

Methods:

An anonymous survey was formulated for adult patients with vascular anomalies, in collaboration with patient advocacy groups. The survey included 50 questions with built-in logic and the entire project received Internal Board Review approval.

Results:

Two-hundred forty-nine surveys were completed and analyzed. Of the participants still receiving care from a pediatric provider, 97% had no plan for transitioning to an adult provider. Of those no longer able to receive care in a pediatric setting, 34% had abandoned searching for a physician willing to provide care and 45% had no consistent care provider for their vascular anomaly. Sixty percent were seeing providers who had no specific interest or training in VAs. Of all respondents, 35% were evaluated in the emergency room due to VA complications at least once in the past year (8% >3 times) and 28% were admitted to the hospital at least once in the past year due to the vascular anomaly (3% >3 times).

Conclusion:

We collected evidence-supported documentation that adults with vascular anomalies are not part of an integrated care plan. Adult trained hematology-oncologists are essential and needed to join the dermatology, surgical, and radiology interdisciplinary teams managing this cohort of patients.
Effect of sodium bicarbonate on functional outcome in patients with out-of-hospital cardiac arrest: a post-hoc analysis of a French and North-American dataset
Authors: Touron Maxime , Javaudin François , Lebastard Quentin , Baert Valentine , Heidet Mathieu , Hubert Hervé , Leclere Brice , Lascarrou Jean-Baptiste ,   for the RéAC Network
Published: March 2022

Background and importance

No large randomised controlled trial has assessed the potential benefits on neurologic outcomes of prehospital sodium bicarbonate administration in patients with nontraumatic out-of-hospital cardiac arrest (OHCA).

Objective

To obtain information of assistance in designing a randomised controlled trial of bicarbonate therapy after OHCA in specific patient subgroups.

Design

We conducted two, separate, simultaneous, retrospective studies of two distinct, unlinked datasets.

Setting and participants

One dataset was a French nationwide population-based registry (RéAC Registry, French dataset) and the other was a randomised controlled trial comparing continuous to interrupted chest compressions in North America (ROC-CCC trial, North-American dataset).

Intervention

We investigated whether prehospital bicarbonate administration was associated with better neurologic outcomes.

Outcome measures and analyses

The main outcome measure was the functional outcome at hospital discharge. To adjust for potential confounders, we conducted a nested propensity-score-matched analysis with inverse probability-of-treatment weighting.

Main results

In the French dataset, of the 54 807 patients, 1234 (2.2%) received sodium bicarbonate and 450 were matched. After propensity-score matching, sodium bicarbonate was not associated with a higher likelihood of favourable functional outcomes on day 30 [adjusted odds ratio (aOR), 0.912; 95% confidence interval (95%CI), 0.501–1.655]. In the North-American dataset, of the 23 711 included patients, 4902 (20.6%) received sodium bicarbonate and 1238 were matched. After propensity-score matching, sodium bicarbonate was associated with a lower likelihood of favourable functional outcomes at hospital discharge (aOR, 0.45; 95% CI, 0.34–0.58).

Conclusion

In patients with OHCA, prehospital sodium bicarbonate administration was not associated with neurologic outcomes in a French dataset and was associated with worse neurologic outcomes in a North-American dataset. Given the considerable variability in sodium bicarbonate use by different prehospital care systems and the potential resuscitation-time bias in the present study, a large randomised clinical trial targeting specific patient subgroups may be needed to determine whether sodium bicarbonate has a role in the prehospital management of prolonged OHCA.
A Method to Identify Intersegmental Planes for Robotic-assisted Anatomic Segmentectomy Without Waiting
Authors: Xu Hao , Chang Xiaoyan , Zhang Linyou
Published: March 2022

Identifying intersegmental planes is considered the key step during segmentectomy. Several techniques, including modified inflation-deflation techniques, target-segment jet ventilation, and infrared-fluorescence-enhanced methods, have been reported for the identification of intersegmental planes. However, limitations of these methods have also been reported. Here, we described an improved collateral ventilation method to identify the inflation-deflation line without waiting and without any auxiliary materials needed during robotic-assisted anatomic segmentectomy. We present this handy technique of identifying the intersegmental planes and comment on its advantages, including decreased operative time and improved clarity of the inflation-deflation line.
Identification of sex chromosome and sex-determining gene of southern catfish (
Silurus meridionalis
) based on XX, XY and YY genome sequencing
Authors: Zheng Shuqing , Tao Wenjing , Yang Haowen , Kocher Thomas D. , Wang Zhijian , Peng Zuogang , Jin Li , Pu Deyong , Zhang Yaoguang , Wang Deshou
Published: March 2022

Teleosts are important models to study sex chromosomes and sex-determining (SD) genes because they present a variety of sex determination systems. Here, we used Nanopore and Hi-C technologies to generate a high-contiguity chromosome-level genome assembly of a YY southern catfish (
Silurus meridionalis
). The assembly is 750.0 Mb long, with contig N50 of 15.96 Mb and scaffold N50 of 27.22 Mb. We also sequenced and assembled an XY male genome with a size of 727.2 Mb and contig N50 of 13.69 Mb. We identified a candidate SD gene through comparisons to our previous assembly of an XX individual. By resequencing male and female pools, we characterized a 2.38 Mb sex-determining region (SDR) on Chr24. Analysis of read coverage and comparison of the X and Y chromosome sequences showed a Y specific insertion (approx. 500 kb) in the SDR which contained a male-specific duplicate of
amhr2
(named
amhr2y
).
amhr2y
and
amhr2
shared high-nucleotide identity (81.0%) in the coding region but extremely low identity in the promotor and intron regions. The exclusive expression in the male gonadal primordium and loss-of-function inducing male to female sex reversal confirmed the role of
amhr2y
in male sex determination. Our study provides a new example of
amhr2
as the SD gene in fish and sheds light on the convergent evolution of the duplication of AMH/AMHR2 pathway members underlying the evolution of sex determination in different fish lineages.
Modified AOAC method for indirect measurement of resistant starch and
its application in development of new food materials
Authors: Lee Jaehoon , So Soonhyun , Kim Charrin , Lee Kangyeon , Park Jongsoon , Lee Deuksik , Lee Deug-chan
Published: March 2022

Resistant starch (RS) is the starch that is not digested by enzymes in the body
and is highly valuable in food. RS functions similar to dietary fiber and is
being studied actively as a raw material for functional health foods. Various
methods have been proposed for the quantification of RS including the
Association of Official Analytical Chemists (AOAC) and Englyst methods. However,
these methods remain to be optimized as their performance depends on the type
and source of the RS being tested. In this study, we used a modified AOAC method
to analyze the RS contents in different food materials. The RS contents was
measured indirectly by both the existing and modified AOAC methods using glucose
from the supernatant and not RS pellets. In addition, we evaluated the modified
method using soybean samples dried in hot air. The modified AOAC and
thiobarbituric acid reactive substance assays indicated that the soybean samples
had a high RS content and showed a low degree of lipid peroxidation. Based on
these results, the modified AOAC method can be considered a simple and accurate
method for analyzing food materials with high RS contents.
Selective Control of Parasitic Nematodes Using Bioactivated Nematicides
Authors: Burns Andrew R. , Ross Rachel J. , Kitner Megan , Volpatti Jonathan R. , Vaidya Aditya S. , Puumala Emily , Palmeira Bruna M. , Redman Elizabeth M. , Snider Jamie , Marwah Sagar , Chung Sai W. , MacDonald Margaret H. , Tiefenbach Jens , Hu Chun , Xiao Qi , Finney Constance A. M. , Krause Henry M. , MacParland Sonya A. , Stagljar Igor , Gilleard John S. , Cowen Leah E. , Meyer Susan L. F. , Cutler Sean R. , Dowling James J. , Lautens Mark , Zasada Inga , Roy Peter J.
Published: March 2022

Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amidst limited arable land. Most traditional nematicides have been banned due to poor nematode-selectivity, leaving farmers with inadequate controls. Here, we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome p450-dependent bioactivation exclusively in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita – the world’s most destructive plant-parasitic nematode. Tests against a wide range of phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than nearly all marketed nematicides. Thus, selectivins are first-in-class bioactivated nematode controls that provide efficacy as well as much-needed nematode selectivity.
cgRNASP: coarse-grained statistical potentials with residue separation for RNA structure evaluation
Authors: Tan Ya-Lan , Wang Xunxun , Yu Shixiong , Zhang Bengong , Tan Zhi-Jie
Published: March 2022

Knowledge-based statistical potentials are very important for RNA 3-dimensional (3D) structure prediction and evaluation. In recent years, various coarse-grained (CG) and all-atom models have been developed for predicting RNA 3D structures, while there is still lack of reliable CG statistical potentials not only for CG structure evaluation but also for all-atom structure evaluation at high efficiency. In this work, we have developed a series of residue-separation-based CG statistical potentials at different CG levels for RNA 3D structure evaluation, namely cgRNASP, which is composed of long-ranged and short-ranged interactions by residue separation. Compared with the newly developed all-atom rsRNASP, the short-ranged interaction in cgRNASP was involved more subtly and completely through explicitly adding the interactions between nearest neighbor residues and between next-nearest ones. Our examinations show that, the performance of cgRNASP varies with CG levels and compared with rsRNASP, cgRNASP can have similarly good performance for extensive test datasets and slightly better performance for the realistic RNA-Puzzles dataset. Furthermore, cgRNASP is strikingly more efficient than all-atom potentials such as rsRNASP, and can be apparently superior to other all-atom statistical potentials and scoring functions trained from neural networks for the RNA-Puzzles dataset. cgRNASP is available at https://github.com/Tan-group/cgRNASP.
Crumbs complex-directed apical membrane dynamics in epithelial cell ingression
Authors: Simões Sérgio , Lerchbaumer Gerald , Pellikka Milena , Giannatou Paraskevi , Lam Thomas , Kim Dohyun , Yu Jessica , Stal David ter , Kakouni Kenana Al , Fernandez-Gonzalez Rodrigo , Tepass Ulrich
Published: March 2022

Epithelial cells often leave their tissue context and ingress to form new cell types or acquire migratory ability to move to distant sites during development and tumor progression. Cell lose their apical membrane and epithelial adherens junctions during ingression. However, how factors that organize apical-basal polarity contribute to ingression is unknown. Here, we show that the dynamic regulation of the apical Crumbs polarity complex is crucial for normal neural stem cell ingression. Crumbs endocytosis and recycling allow ingression to occur in a normal timeframe. During early ingression, Crumbs and its complex partner the RhoGEF Cysts support myosin and apical constriction to ensure robust ingression dynamics. During late ingression, the E3-ubiquitin ligase Neuralized facilitates the disassembly of the Crumbs complex and the rapid endocytic removal of the apical cell domain. Our findings reveal a mechanism integrating cell fate, apical polarity, endocytosis, vesicle trafficking, and actomyosin contractility to promote cell ingression, a fundamental morphogenetic process observed in animal development and cancer.
Probiotic responder identification in cross-over trials for constipation using a Bayesian statistical model considering lags between intake and effect periods
Authors: Hosoda Shion , Nishimoto Yuichiro , Yamauchi Yohsuke , Yamada Takuji , Hamada Michiaki
Published: March 2022

Recent advances in microbiome research have led to the further development of microbial interventions, such as probiotics and prebiotics, which are potential treatments for constipation. However, the effects of probiotics vary from person to person; therefore, the effectiveness of probiotics needs to be verified for each individual. Individuals showing significant effects of the target probiotic are called responders. A statistical model for the evaluation of responders was proposed in a previous study. However, the previous model does not consider the lag between intake and effect periods of the probiotic. It is expected that the lag exists when probiotics are administered and when they are effective. In this study, we propose a Bayesian statistical model to estimate the probability that a subject is a responder, by considering the lag between intake and effect periods. In synthetic dataset experiments, the proposed model was found to outperform the base model, which did not factor in the lag. Further, we found that the proposed model could distinguish responders showing large uncertainty in terms of the lag between intake and effect periods.