bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological Study of Stylomastoid Foramen at the Base of Skull and its Role in Facial Nerve Palsy
Authors: Singh Rajani
Published: May 2023

The facial nerve emerges out of skull through the stylomastoid foramen located between styloid process and mastoid process. Unilateral paralysis of facial nerve is known as Bell’s palsy and is reported to be caused most frequently by herpes simplex virus. The herpes infection is comparatively common but Bell’s palsy is not very common. So, other causes of Bell’s palsy like variation in morphological forms of stylomastoid cannot be ruled. There is paucity of literature elucidating morphological shapes of this foramen and correlating these forms of foramen with Bell’s palsy. Hence the study was carried out. The aim of this study is to expound varied forms of stylomastoid foramen and to bring out clinical implications. The study was conducted in the department of anatomy using undamaged 70 adult dry human skulls of unknown age and sex. The morphological shapes were observed, interpretated and compared with available literature and their clinical implications were brought out. Most common shapes observed were round and oval followed by square shapes. Round shaped foramina were observed in 40 skulls on right sides constituting 57.1% and in 36 skulls on left side constituting 51.4%. While oval shapes were found in 16 skulls on right side (22.6%) and in 12 skulls on left side (17.1%). Rare variants of the foramen include triangular, serrated and closely applied to styloid process. The rare morphological forms were mostly observed to be unilateral in occurrence. Unilateral Bell’s palsy is common, so, the rare morphological forms might be responsible for Bell’s palsy.
Assessment of Skeletal Maturation in Nonsyndromic Cleft and Non-cleft Children—A Comparative Study
Authors: Qureshi Tabassum , Kharbanda Om Prakash , Duggal Ritu
Published: May 2023

The study aims to determine the difference in the skeletal maturation of unilateral cleft lip and palate (UCLP) and non-cleft children. This study also attempts to determine sexual dimorphism in attaining skeletal maturation between UCLP and non-cleft children. This was a retrospective, cross-sectional study. The total sample consisted of the lateral cephalogram of 131 UCLP (62 female and 71 male) children and 500 (274 female and 226 male) non-cleft children. The reviewer used the Baccetti method (2005) to review all the cephalograms for the cervical vertebrae maturation (CVM) stages. T-test was used to compare the mean chronological age and skeletal maturation of cleft and non-cleft children at each CVM stage. There was no significant difference in the mean chronological age and skeletal maturation status of UCLP and non-cleft children. There was no significant difference in skeletal maturation based on sex. The intraobserver assessment showed 80% and 85% kappa agreement, signifying absolute agreement. The correlation coefficient between chronological age and CVMIs was 0.86 (P<0.001) in cleft children and 0.76 (P<0.001) in non-cleft children, which was highly significant. The study indicates no significant difference in the skeletal maturation of UCLP and non-cleft children and no sex-related difference.
Predictors of Surgical Versus Medical Management of Eyes in the Setting of Orbital Fracture at an Academic Level I Trauma Center
Authors: Yan Maria , Mullen Barbara , Wagner Lilly H. , Bradley Elizabeth , Tooley Andrea A. , Sharaf Basel A
Published: May 2023

We present clinical and imaging predictors of ocular injuries that required medical management versus surgical intervention in cases of orbital fractures. From 2014 to 2020, a retrospective review of patients with orbital fractures who received ophthalmologic consultation and computed scan (CT) analysis at a level I trauma center was performed. Inclusion criteria were patients with confirmed orbital fracture on CT and ophthalmology consultation. Patient demographics, associated injuries, comorbidities, management, and outcomes were collected. Two hundred and one patients and 224 eyes (11.4% bilateral orbital fractures) were included. Overall, 21.9% of orbital fractures presented with a significant concomitant ocular injury. Associated facial fractures were present in 68.8% of eyes. Management included surgical treatment in 33.5% of eyes and ophthalmology-directed medical treatment in 17.4%. On multivariate analysis, clinical predictors of surgical intervention were retinal hemorrhage (OR=4.7 (1.0–21.0), P=0.0437), motor vehicle accident injury (OR=2.7 (1.4–5.1), P=0.0030) and diplopia (OR=2.8 (1.5–5.3), P=0.0011). Imaging predictors of surgical intervention were herniation of orbital contents (OR=2.1 (1.1–4.0), P=0.0281) and multiple wall fractures (OR=1.9 (1.01–3.6), P=0.0450). Predictors of medical management were corneal abrasion (OR=7.7 (1.9–31.4), P=0.0041), periorbital laceration (OR=5.7 (2.1–15.6), P=0.0006), and traumatic iritis (OR=4.7 (1.1–20.3), P=0.0444). We demonstrated a 22% incidence of concomitant ocular trauma in orbital fracture patients at our level I trauma center. Predictors of the surgical intervention included multiple wall fractures, herniation of orbital contents, retinal hemorrhage, diplopia, and motor vehicle accident injury. These findings emphasize the importance of a multidisciplinary team in managing ocular and facial trauma.
Spinal Muscular Atrophy Type III Recognized After Delayed Recovery From Neuromuscular Blockade After an Orthognathic Surgery
Authors: Oda Aya , Oue Kana , Yoshida Mitsuhiro
Published: May 2023

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by the degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. SMA is classified into types I-IV based on the age at symptom onset or maximum motor function achieved, and its clinical manifestations vary. SMA affects maxillofacial growth because of muscle dysfunction and results in abnormal maxillofacial morphology. In addition, definitive diagnosis is not often made because of the older onset age and symptoms are rarely severe. Therefore, the possibility of undiagnosed SMA in craniofacial surgeries must be considered. This report described a case of an SMA type III recognized after delayed recovery from the neuromuscular blockade in an orthognathic surgery under general anesthesia.
Risk Factors for Maxillofacial Space Infection Complications: A Retrospective Analysis of 457 Patients
Authors: Li Peijun , He Yang , Zhang Yi , An Jingang , Yang Yue
Published: May 2023

This study was performed to determine the risk factors associated with systemic complications of maxillofacial space infection (MSI), and to propose an objective evaluation index - severity score of MSI. 457 MSI patients from Jan 2010 to Dec 2020 were reviewed retrospectively. The predictor variables included demographic, origin of infection, underlying systemic disease, pre-hospital medication history, laboratory examinations and severity scores of space infection. The severity score of space infection was proposed to evaluate the airway compromise of anatomic spaces. The primary outcome variable was the complication. The impact factors of complications were analyzed using univariate analysis and multivariate logistic regression. 457 patients were included (average age 46.3 y, male to female ratio 1.43:1). Among them, 39 patients developed postoperative complications. In the complication group, there were 18 patients (46.2%) with pulmonary infection, and two patients died. We found that the history of diabetes mellitus (OR=4.74, 95% confidence interval (CI)=2.22, 10.12), high temperature (≥39°C) (OR=4.16, 95% CI=1.43, 12.06), advanced age (≥65 y) (OR=2.88, 95% CI=1.37, 6.01), and severity score of space infection (OR=1.14, 95% CI=1.04, 1.25) were independent risk factors for complications of MSI. All the risk factors needed to be closely monitored. Severity score of MSI was an objective evaluation index to predict complications.
One-Abutment at One-Time in Posterior Edentulism: A Systematic Review and Meta-Analysis
Authors: Kang Yujie , Zheng Xianghuai , Zhang Danya , Li Shaobing , Xu Shulan , Chen Lei , Zhang Zhaoqiang , Lin Xi
Published: May 2023

Objective:

The objective of this systematic review and meta-analysis was to investigate the clinical significance of one-abutment at one-time protocol in healed posterior edentulism.

Methods:

An online search was undertaken in November 2022, which included PubMed, Cochrane Library, Wiley Online Library, and Google Scholar in addition to manual searching. The Cochrane Collaboration tool was performed to assess the quality of selected articles. Marginal bone loss (MBL) was estimated by the performance of meta-analysis. Moreover, all the pooled analyses were based on random-effect models. Subgroup analysis was applied to evaluate the effects of different variables.

Results:

In line with the inclusion criteria, 6 trials with 446 dental implants were identified. The meta-analysis showed a total of 0.22 mm less MBL within 6 months and decreased by 0.30 mm at 1-year follow-up in favor of one-abutment at one-time protocol. A significant loss MBL was found in implants placed equicrestally using one-abutment at one-time protocol [6 months: mean difference (MD): −0.22 mm; 95% CI, −0.34 to 0.10 mm, P=0.0004; 12 months: MD: −0.32 mm; 95% CI, −0.40 to −0.24 mm, P<0.00001), whereas no difference was found between 2 groups in an implant placed subscrestally (6 months: MD: 0.14 mm; 95% CI, −0.03 to 0.22 mm; P=0.11; 12 months: MD: −0.12 mm; 95% CI, −0.32 to 0.08 mm; P=0.23).

Conclusions:

Implant platform position might greatly affect the marginal bone level. Moreover, one-abutment at one-time protocol demonstrated better bone preservation in implants placed equicrestally in healed posterior edentulism.

Clinical Relevance:

This study highlights the significant clinical application of one-abutment at one-time protocol in healed posterior edentulism.
External Z-plasty Technique for Correction of Alar Retraction in Asian Patients
Authors: Yu Bao-Fu , Zhu Hai-Jun , Chen Xiao-Xue , Wang Zi , Dai Chuan-Chang , Wei Jiao
Published: May 2023

Background:

Current strategies for correcting alar retraction mainly include cartilage grafting and composite grafting, which are relatively complicated and may produce injury to the donor site. Herein, we introduce a simple and effective external Z-plasty technique for correcting alar retraction in Asian patients with poor skin malleability.

Methods:

Twenty-three patients were presented with alar retraction and poor skin malleability, and they were very concerned about the shape of the nose. These patients undergoing external Z-plasty surgery were analyzed retrospectively. In this surgery, no grafts were needed, and the location of the Z-plasty was according to the highest point of the retracted alar rim. We reviewed the clinical medical notes and photographs. During the postoperative follow-up period, patients’ reported satisfaction with aesthetic outcome were also evaluated.

Results:

The alar retraction of all the patients was successfully corrected. The postoperative mean follow-up period was 8 months (range: 5–28 mo). No incidents of flap loss, recurrence of alar retraction, or nasal obstruction were observed during postoperative follow-up. Within postoperative 3–8 weeks, minor red scarring was visible at the operative incisions in most patients. However, these scars turned unobvious after postoperative 6 months. There were 15 cases (15/23) being very satisfied with the aesthetic outcome of this procedure. Seven patients (7/23) were satisfied with the effect and the invisible scar of this operation. Only one patient was dissatisfied with the scar, but she was satisfied with the correction effect of the retraction.

Conclusion:

This external Z-plasty technique can be an alternative method for correction of alar retraction with no need of cartilage grafting, and the scar can be unobvious with fine surgical suture. However, the indications should be limited in patients with severe alar retraction and poor skin malleability, who should not particularly care about the scars.
NUCLEOLIN PROMOTES AUTOPHAGY THROUGH PGC-1Α IN LPS-INDUCED MYOCARDIAL INJURY
Authors: Yin Leijing , Yuan Ludong , Tang Yuting , Luo Zhengyang , Lin Xiaofang , Wang Shuxin , Liang Pengfei , Jiang Bimei
Published: May 2023

As a multifunctional protein, nucleolin can participate in a variety of cellular processes. Nucleolin also has multiple protective effects on heart disease. Previous studies have shown that nucleolin could not only resist oxidative stress damage and inflammatory damage, but also regulate autophagy to play a protective role in cardiac ischemia. However, the specific mechanism has not been fully elucidated in LPS-induced myocardial injury. Therefore, the aim of this study is to explore the underlying mechanism by which nucleolin regulates autophagy to protect against LPS-induced myocardial injury in vivo and in vitro. In our study, we found that nucleolin could bind to PGC-1α, and we predicted that this interaction could promote autophagy and played a role in inhibiting cardiomyocyte apoptosis. Downregulation of nucleolin in H9C2 cells resulted in decreased autophagy and increased cell apoptosis during LPS-induced myocardial injury, while upregulation of PGC-1α had the opposite protective effect. Upregulation of nucleolin expression in cardiomyocytes could increase the level of autophagy during LPS-induced myocardial injury. In contrast, interference with PGC-1α expression resulted in a decrease in the protective effect of nucleolin, leading to reduced autophagy and thus increasing apoptosis. By using tandem fluorescent-tagged LC3 autophagic flux detection system, we observed autophagic flux and determined that PGC-1α interference could block autophagic lysosomal progression. We further tested our hypothesis in the nucleolin cardiac-specific knockout mice. Finally, we also found that inhibition of autophagy can reduce mitochondrial biogenesis as well as increase apoptosis, which demonstrated the importance of autophagy. Therefore, we can speculate that nucleolin can protect LPS-induced myocardial injury by regulating autophagy, and this protective effect may be mediated by the interaction with PGC-1α, which can positively regulate the ULK1, an autophagy-related protein. Our study provides a new clue for the cardioprotective effect of nucleolin, and may provide new evidence for the treatment of LPS-induced myocardial injury through the regulation of autophagy.
Caregiver Burden and Quality of Life Across Alzheimer’s Disease Severity Stages
Authors: van Hezik-Wester Valérie J. , Handels Ron L.H. , Wolfs Claire A.G. , Kanters Tim A.
Published: May 2023

Introduction:

The objective is to estimate the caregiver burden in terms of informal care time, health-related quality of life (HRQoL), and societal costs by disease severity (mild, moderate, or severe) and living situation (community-dwelling or institutionalized) of persons with AD (PwAD); and PwAD HRQoL.

Methods:

Caregivers were recruited through an online panel provider in the Netherlands. The survey used validated instruments, including iMTA Valuation of Informal Care Questionnaire, CarerQoL, and EQ-5D-5L.

Results:

One hundred two caregivers participated. PwADs received, on average, 26 hours of informal care per week. Informal care costs were higher for community-dwelling PwADs compared with institutionalized PwADs (€480 and €278, respectively). On the EQ-5D-5L, caregivers scored on average 0.797, reflecting a utility decrement of 0.065 compared with an age-matched population. Proxy-rated utility scores for PwADs decreased with increasing disease severity (0.455, 0.314, and 0.212 for mild, moderate, and severe AD, respectively). Institutionalised PwADs had lower utility scores than community-dwelling PwADs (0.590 vs. 0.421). There was no difference in informal care time, societal costs, CarerQol scores, and caregiver EQ-5D-5L scores between disease severities.

Conclusion:

The burden of AD extends to caregivers in terms of HRQoL and time investment, regardless of the disease severity of the target population. These impacts should be incorporated into the evaluation of new AD interventions.
Grandmother presence improved grandchild survival against childhood infections but not vaccination coverage in historical Finns
Authors: Ukonaho Susanna , Chapman Simon N. , Briga Michael , Lummaa Virpi
Published: May 2023

Grandmother presence can improve the number and survival of their grandchildren, but what grandmothers protect against and how they achieve it remains poorly known. Before modern medical care, infections were leading causes of childhood mortality, alleviated from the nineteenth century onwards by vaccinations, among other things. Here, we combine two individual-based datasets on the genealogy, cause-specific mortality and vaccination status of eighteenth- and nineteenth-century Finns to investigate two questions. First, we tested whether there were cause-specific benefits of grandmother presence on grandchild survival from highly lethal infections (smallpox, measles, pulmonary and diarrhoeal infections) and/or accidents. We show that grandmothers decreased all-cause mortality, an effect which was mediated through smallpox, pulmonary and diarrhoeal infections, but not via measles or accidents. Second, since grandmothers have been suggested to increase vaccination coverage, we tested whether the grandmother effect on smallpox survival was mediated through increased or earlier vaccination, but we found no evidence for such effects. Our findings that the beneficial effects of grandmothers are in part driven by increased survival from some (but not all) childhood infections, and are not mediated via vaccination, have implications for public health, societal development and human life-history evolution.
Evolutionary rescue in a fluctuating environment: periodic versus quasi-periodic environmental changes
Authors: Marrec Loïc , Bank Claudia
Published: May 2023

No environment is constant over time, and environmental fluctuations impact the outcome of evolutionary dynamics. Survival of a population not adapted to some environmental conditions is threatened unless, for example, a mutation rescues it, an eco-evolutionary process termed evolutionary rescue. We here investigate evolutionary rescue in an environment that fluctuates between a favourable state, in which the population grows, and a harsh state, in which the population declines. We develop a stochastic model that includes both population dynamics and genetics. We derive analytical predictions for the mean extinction time of a non-adapted population given that it is not rescued, the probability of rescue by a mutation, and the mean appearance time of a rescue mutant, which we validate using numerical simulations. We find that stochastic environmental fluctuations, resulting in quasi-periodic environmental changes, accelerate extinction and hinder evolutionary rescue compared with deterministic environmental fluctuations, resulting in periodic environmental changes. We demonstrate that high equilibrium population sizes and per capita growth rates maximize the chances of evolutionary rescue. We show that an imperfectly harsh environment, which does not fully prevent births but makes the death rate to birth rate ratio much greater than unity, has almost the same rescue probability as a perfectly harsh environment, which fully prevents births. Finally, we put our results in the context of antimicrobial resistance and conservation biology.
Yinghuangia soli sp. nov., isolated from soil of weathering dolomite in a karst area
Authors: Yao Jiaqi , Zhang Ya , Gao Yuan , Liu Lingxiao , Ma Zhouai , Cao Chengliang , Li Ludan , Jiang Jihong , Liu Jinjuan
Published: May 2023

A Gram-stain-positive, aerobic actinomycete strain, designated KLBMP 8922T, was isolated from a soil sample collected from weathering dolomite crust in Guizhou Province, PR China. KLBMP 8922T showed the 16S rRNA gene similarities to

Yinghuangia seranimata

CCTCC AA 206006T (98.7 %),

Yinghuangia catbensis

VN07A0015T (98.3 %) and

Yinghuangia aomiensis

M24DS4T (98.2 %). The taxonomic status of this strain was investigated by using a polyphasic approach. The aerial mycelia of KLBMP 8922T formed spore chains, and spores were cylindrical with smooth surfaces. The whole-cell sugars were ribose, mannose and galactose with traces of glucose and xylose. The diagnostic amino acids of the cell wall were ll-diaminopimelic acid, alanine and glutamic acid. The predominant menaquinones were MK-9(H6) and MK-9(H8). The diagnostic phospholipids were diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositolmannoside, phosphatidylethanolamine, an unidentified phospholipid and an unidentified lipid. The major cellular fatty acids (>10 %) were iso-C15 : 0, iso-C16 : 0 and iso-C16 : 1H. The genomic DNA G+C content was 72.0 mol%. The digital DNA–DNA hybridization (dDDH) value between KLBMP 8922T and

Y. seranimata

CCTCC AA 206006T was 24.1 %, and the average nucleotide identity (ANI) value was 81.0 %. On the basis of a combination of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 8922T represents a novel species of the genus

Yinghuangia

for which the name Yinghuangia soli sp. nov. is proposed. The type strain was KLBMP 8922T (= CGMCC 1.19360T = NBRC 115572T).
AadT, a new weapon in Acinetobacter’s fight against antibiotics
Authors: Naidu Varsha , Shah Bhumika , Maher Claire , Paulsen Ian T. , Hassan Karl A.
Published: May 2023

Genes encoding a novel multidrug efflux pump, AadT, from the Drug:H+ antiporter 2 family, were discovered in

Acinetobacter

multidrug resistance plasmids. Here, we profiled the antimicrobial resistance potential, and examined the distribution of these genes. aadT homologs were found in many

Acinetobacter

and other Gram-negative species and were typically adjacent to novel variants of adeAB(C), which encodes a major tripartite efflux pump in

Acinetobacter

. The AadT pump decreased bacterial susceptibility to at least eight diverse antimicrobials, including antibiotics (erythromycin and tetracycline), biocides (chlorhexidine), and dyes (ethidium bromide and DAPI) and was able to mediate ethidium transport. These results show that AadT is a multidrug efflux pump in the

Acinetobacter

resistance arsenal and may cooperate with variants of AdeAB(C).
A Deep Learning Approach to Accurately Discriminate Between Optic Disc Drusen and Papilledema on Fundus Photographs
Authors: Sathianvichitr Kanchalika , Najjar Raymond P. , Zhiqun Tang , Fraser J. Alexander , Leng Yau Christine Wen , Girard Michael Julien Alexandre , Costello Fiona , Lin Mung Yan , Lagrèze Wolf Alexander , Vignal-Clermont Catherine , Fraser Clare L. , Hamann Steffen , Newman Nancy J. , Biousse Valérie , Milea Dan ,   the BONSAI Group
Published: May 2023

Objective

To assess the performance of a deep learning system (DLS) to discriminate between optic disc drusen (ODD) and papilledema caused by intracranial hypertension, using standard color ocular fundus photographs collected in a large international multi-ethnic population.

Design

Retrospective study.

Participants

The study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group.

Methods

We trained, validated, and tested a dedicated DLS for binary classification of ODD vs. papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External-testing was subsequently performed on an independent dataset (221 patients) including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study.

Main outcome measures

Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to discriminate between ODD and papilledema.

Results

Overall, the DLS could accurately distinguish between all ODD and papilledema (all severities included): AUC 0.97 (95% confidence interval [CI], 0.96 to 0.98), accuracy 90.5% (95% CI, 88.0% to 92.9%), sensitivity 86.0% (95% CI, 82.1% to 90.1%), and specificity 94.9% (95% CI, 92.3% to 97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90 to 0.96), accuracy 84.2% (95% CI, 80.2%-88.6%), sensitivity 78.4% (95% CI, 72.2% to 84.7%), and specificity 91.3% (95% CI, 87.0% to 96.4%).

Conclusions

A dedicated DLS can accurately distinguish between ODD and papilledema caused by elevated intracranial pressure, even when considering buried ODD vs mild-to-moderate papilledema. Future studies are required to validate the utility of this DLS in clinical practice.
Bridging Gaps: Improving access to general practice for and with marginalised patients- “it’s quite joyful for us, it’s really improved our work”
Authors: Potter Lucy C , Stone Tracey , Swede Julie ,   BG group, Connell Florrie , Cramer Helen , McGeown Helen , Carvalho Maria , Horwood Jeremy , Feder Gene , Farr Michelle
Published: May 2023

Background

People with severe and multiple disadvantage (SMD-combinations of homelessness, substance misuse, violence, abuse and poor mental health) have high health needs and poor access to primary care.

Aim

To explore perceptions and experiences of improving access to general practice for people with SMD in healthcare staff and people with lived experience.

Design and Setting

Bridging Gaps is a collaboration between healthcare staff, researchers, women with lived experience of SMD and a charity that supports them in a UK city. We co-produced a project to improve access to general practice for marginalised patients, that was further developed with 3 inner city general practices.

Method

We observed six collaborative service improvement meetings at three general practices and conducted documentary analysis of minutes of a further three meetings. We interviewed nine practice staff and four participants with lived experience. Three participants with lived experience and one staff member who supports them participated in a focus group. Data was analysed inductively and deductively using thematic analysis.

Results

Enabling motivated general practice staff with time and funding opportunities, galvanised by lived experience involvement, resulted in sustained service changes. These included: care coordinators and patient lists to support access to patients in greater need and an information sharing tool. The process and outcomes improved connections within and between general practices, support organisations and marginalised patients.

Conclusion

These co-produced strategies could be locally adapted and evaluated elsewhere. Investing in this different way of working may improve inclusion of marginalised groups, health equity and staff wellbeing.

How this fits in

This study builds on previous work showing that continuity of care, being able to develop a trusting relationship and being proactive are of particular importance in providing care to highly marginalised patients(4, 5, 6, 7, 8). This work describes co-produced strategies including using care coordinators, patient lists and an information sharing tool to support access and continuity to patients in greater need, in addition to rich contextual information on how to shift ways of working to achieve this. In addition to a small team focused on marginalised patients, this study supports the literature highlighting the need for a trauma-informed approach throughout the whole practice team. These co-produced strategies could be adapted and piloted in other practices and areas. Investing in this focused way of working may improve inclusion of marginalised groups, health equity and staff wellbeing.
Non-Invasive markers of inflammation and protein loss augment diagnosis of celiac disease
Authors: Sutton Kimberly A , He Mai , Ma Changqing , Liu Ta-Chiang , Faubion William A. , Hoffman Julie , Linneman Laura , Rodriguez Cynthia , Holtz Lori R
Published: May 2023

Background

Circulating tissue transglutaminase IgA (TTG IgA) concentrations are sensitive and specific indicators of celiac disease, but discrepancies between serologic and histologic findings still occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as non-invasive means of evaluating disease activity.

Methods

Participants with positive celiac serologies and controls with negative celiac serologies were enrolled at the time of upper endoscopy. Blood, stool and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin and alpha-1-antitrypsin and plasma lipcalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and TTG IgA concentration.

Results

Lipocalin-2 was significantly elevated in the stool (p=0.007) but not the plasma of participants with positive celiac serologies compared to controls. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100mg/dL was specific, but not sensitive for biopsy proven celiac disease.

Conclusions

Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role in the local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease and did not correlate with degree of histologic changes on biopsy. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared to controls, an elevation of greater than 100mg/dL was 90% specific for biopsy proven celiac disease.
Association between lifestyle factors and weight in Japan university students during COVID-19 mild lockdown: a quantitative study
Authors: Arimori Haruka , Abiru Norio , Morimoto Shimpei , Nishino Tomoya , Kawakami Atsushi , Kamada Akie , Kobayashi Masakazu
Published: May 2023

We investigated the lifestyle factors influencing weight gain in university students during restrictions (mild lockdown) imposed owing to the novel coronavirus disease pandemic in Japan. In this cross-sectional study, a questionnaire survey of Nagasaki University students undergoing health examinations was conducted in 2021. Students reporting ≥3 kg weight gain were included in the weight gain group; the remaining students were in the non-weight gain group. Fisher’s exact test and binary logistic regression were performed to detect the associations between weight gain and each lifestyle factor. We included 3,059 respondents (response rate: 45.7%), and 9.5% respondents reported ≥3 kg weight gain. The following factors were associated with weight gain (odds ratio, 95% confidence interval, p value from Fisher’s exact test): dining out for ≥4 times/week (2.16 [1.40, 3.32], p = 8.7 × 10−4), gaming time of ≥4 h/day (2.26 [1.45, 3.47], p = 2.4 × 10−4). Binary logistic regression among the four highest odds ratios showed that after adjusting for other factors frequently dining out and prolonged gaming time were significantly associated with weight gain. Prolonged gaming and frequently dining out were associated with weight gain in students during the mild lockdown.
Patient Risk-Benefit Preferences for Transcatheter versus Surgical Mitral Valve Repair
Authors: Hung Anna , Yang Jui-Chen , Wallace Matthew , Zwischenberger Brittany A. , Vemulapalli Sreekanth , Mentz Robert J. , Thoma Elizabeth , Goates Scott , Lewis John , Strong Susan , Reed Shelby D.
Published: May 2023

BACKGROUND

Transcatheter repair of mitral regurgitation (MR) is less invasive than surgery, but has greater five-year mortality and re-intervention risks, as well as more limited functioning. The study objective was to quantify patient preferences for risk-benefit tradeoffs associated with transcatheter and surgical options for MR.

METHODS

A discrete-choice experiment survey was administered to patients with MR recruited through a patient advocacy organization. Attributes (and levels) included: procedure type (transcatheter versus surgical); risk of 30-day mortality (2%, 5%, and 10%); risk of five-year mortality (20%, 30%, and 45%) and physical functioning for five years (corresponding to improvements from New York Heart Association [NYHA] class III to I or class III to II); number of hospitalizations (1, 4, and 8) in the next five years; and risk of additional surgery in the next five years (10%, 20%, and 30% or 40%). A mixed-logit regression model was fit to estimate preference weights.

RESULTS

201 individuals completed the survey: 63% were female; mean age was 74 years. On average, respondents preferred transcatheter repair over surgery. To undergo a less invasive procedure (i.e., transcatheter repair), respondents would accept up to a 13.3% (95% confidence interval [CI]: 8.7% to 18.5%) increase in re-intervention risk above a baseline of 10%, 4.6 (95% CI: 3.1 to 6.2) more hospitalizations above a baseline of one, a 9.3% (95% CI: 5.2% to 14.3%) increase in mortality risk above a baseline of 20%, or more limited physical functioning representing nearly one NYHA class (0.8, 95% CI: 0.5 to 1.3) over five years.

CONCLUSIONS

Patients in general preferred a transcatheter procedure over surgery. When holding constant all other factors, a functional improvement from NYHA class III to class I maintained over five years would be needed, on average, for patients to prefer surgery over a transcatheter procedure.
Microhabitat use of northern and southern flying squirrels in a recent hybrid zone
Authors: O’Brien Paul P , Bowman Jeff , Newar Sasha , Garroway Colin J
Published: May 2023

Secondary contact of closely related species may lead to hybridization if reproductive isolation is incomplete. Selection against hybrids may become reinforced if hybrid fitness is low. This can be evident from the divergence of isolating traits. We examined habitat use of northern (Glaucomys sabrinus(Shaw, 1801)) and southern (Glaucomys volans(Linnaeus, 1758)) flying squirrels in an area of secondary contact in Ontario, Canada. We looked at summer microhabitat use within sites of sympatry and allopatry to test for evidence of reinforcement due to diverging habitat use. We also examined differences in broad-scale habitat features at woodlots to determine predictors of species occurrence across sites. We used 18 years (2002 - 2019) of flying squirrel summer capture data from 6 sites along a north-south transect. Vegetation surveys were conducted at trap locations during summer 2016 to characterize the available microhabitats within sites. Site-level habitat variables were calculated using the collected microhabitat variables. We found microhabitat variables to be weak predictors of trap-level flying squirrel presence and we found no evidence of divergence in microhabitat use over the 18 years. Further, we found latitude, not broad-scale habitat, was the strongest predictor of site-level flying squirrel occurrence. Overall, our findings suggest that microhabitat-based isolation is not being reinforced between flying squirrels; however, hybridization may be limited to areas where climate and habitat is suitable for both species.
Signaling mechanisms and agricultural applications of (Z)-3-Hexenyl Butyrate-mediated stomatal closure
Authors: Payá Celia , Belda-Palazón Borja , Vera-Sirera Francisco , Pérez-Pérez Julia , Jordá Lucía , Rodrigo Ismael , Bellés José M , López-Gresa M Pilar , Lisón Purificación
Published: May 2023

Biotic and abiotic stresses can severely limit crop productivity. In response to drought, plants close stomata to prevent water loss. Besides, stomata are considered the main entrance of several pathogens. Therefore, the development of natural products to control stomata closure can be considered a sustainable strategy to cope with stresses in agriculture. Plants respond to different stresses by releasing volatile organic compounds (VOCs). Green leaf volatiles (GLVs), which are commonly produced across different plant species after tissue damage, comprise an important group within VOCs. Among them, (Z)-3-hexenyl butyrate (HB) was described as a natural inducer of stomatal closure, playing an important role in stomatal immunity, although its mechanism of action is still unknown. Here, through different genetic, pharmacological, and biochemical approaches, we uncover that HB perception initiates various defense signaling events such as activation of Ca2+permeable channels, mitogen-activated protein kinases (MPKs) and production of NADPH oxidase-mediated reactive oxygen species (ROS). Furthermore, HB-mediated stomata closure resulted to be independent of abscisic acid (ABA) biosynthesis and signaling. Additionally, exogenous treatments with HB alleviate water stress and improve fruit productivity in tomato plants. The efficacy of HB was also tested under open field conditions, leading to enhanced resistance againstPhytophthoraspp. andPseudomonas syringaeinfection in potato and tomato plants, respectively. Taken together, our results provide insights into HB signaling transduction pathway, confirming its role in stomatal closure and plant immune system activation, and proposing HB as a new phytoprotectant for the sustainable control of biotic and abiotic stresses in agriculture.
No Replication of Direct Neuronal Activity-related (DIANA) fMRI in Anesthetized Mice
Authors: Choi Sang-Han , Im Geun Ho , Choi Sangcheon , Yu Xin , Bandettini Peter A. , Menon Ravi S. , Kim Seong-Gi
Published: May 2023

Toi et al. (Science, 378, 160-168, 2022) reported direct imaging of neuronal activity (DIANA) by fMRI in anesthetized mice at 9.4 T, which could be a revolutionary approach for advancing systems neuroscience research. There have been no independent replications of this observation to date. We performed fMRI experiments in anesthetized mice at an ultrahigh field of 15.2 T using the identical protocol as in their paper. The BOLD response to whisker stimulation was reliably detected in the primary barrel cortex before and after DIANA experiments; however, no direct neuronal activity-like fMRI peak was observed in individual animals’ data with the 50–300 trials used in the DIANA publication. Extensively averaged data involving 1,050 trials in 6 mice (1,050×54 = 56,700 stimulus events) and having a temporal signal-to-noise ratio of 7,370, showed a flat baseline and no detectable neuronal activity-like fMRI peak. Thus we were unable to replicate the previously reported results using the same methods, despite a much higher number of trials, a much higher temporal signal-to-noise ratio, and a much higher magnetic field strength. We were able to demonstrate spurious, non-replicable peaks when using a small number of trials. It was only when performing the inappropriate approach of excluding outliers not conforming to the expected temporal characteristics of the response did we see a clear signal change; however, these signals were not observed when such a outlier elimination approach was not used.
Compositional analysis of microbiome data using the linear decomposition model (LDM)
Authors: Hu Yi-Juan , Satten Glen A.
Published: May 2023

There are compelling reasons to test compositional hypotheses about microbiome data. We present here LDM-clr, an extension of our linear decomposition model (LDM) approach to allow fitting linear models to centered-log-ratio-transformed taxa count data. As LDM-clr is implemented within the existing LDM program, it enjoys all the features supported by LDM, including a compositional analysis of differential abundance at both the taxon and community levels, while allowing for a wide range of covariates and study designs for either association or mediation analysis.

Availability and Implementation

LDM-clr has been added to the R package LDM, which is available on GitHub athttps://github.com/yijuanhu/LDM.

Contact

yijuan.hu@emory.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Biochemical, biomarker, and behavioral characterization of theGrnR493Xmouse model of frontotemporal dementia
Authors: Smith Denise M. , Aggarwal Geetika , Niehoff Michael L. , Jones Spencer A. , Banerjee Subhashis , Farr Susan A. , Nguyen Andrew D.
Published: May 2023

Heterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, theGrnR493Xmouse model has not been characterized completely. Additionally, while homozygousGrnR493XandGrnknockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygousGrnR493Xknockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygousGrnR493Xmice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. HeterozygousGrnR493Xmice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits inGrnR493Xmice that mirror those observed inGrnknockout mouse models, as well as impairment in memory and executive function. Overall, theGrnR493Xknockin mouse model closely phenocopiesGrnknockout models. Lastly, in contrast to homozygous knockin mice, heterozygousGrnR493Xmice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use thisGrnknockin mouse model and otherGrnknockout models.
Pseudouridine guides germline small RNA transport and epigenetic inheritance
Authors: Herridge Rowan P , Dolata Jakub , Migliori Valentina , de Santis Alves Cristiane , Borges Filipe , Schorn Andrea J , Van Ex Frédéric , Parent Jean-Sebastien , Lin Ann , Bajczyk Mateusz , Leonardi Tommaso , Hendrick Alan , Kouzarides Tony , Martienssen Robert A
Published: May 2023

Epigenetic modifications that arise during plant and animal development, such as DNA and histone modification, are mostly reset during gamete formation, but some are inherited from the germline including those marking imprinted genes1. Small RNAs guide these epigenetic modifications, and some are also inherited by the next generation2,3. InC. elegans, these inherited small RNAs have poly (UG) tails4, but how inherited small RNAs are distinguished in other animals and plants is unknown. Pseudouridine (Ψ) is the most abundant RNA modification but has not been explored in small RNAs. Here, we develop novel assays to detect Ψ in short RNA sequences, demonstrating its presence in mouse andArabidopsismicroRNAs and their precursors. We also detect substantial enrichment in germline small RNAs, namely epigenetically activated siRNAs (easiRNAs) inArabidopsispollen, and piwi-interacting piRNAs in mouse testis. In pollen, pseudouridylated easiRNAs are localized to sperm cells, and we found thatPAUSED/HEN5 (PSD), the plant homolog of Exportin-t, interacts genetically with Ψ and is required for transport of easiRNAs into sperm cells from the vegetative nucleus. We further show that Exportin-t is required for the triploid block: chromosome dosage-dependent seed lethality that is epigenetically inherited from pollen. Thus, Ψ has a conserved role in marking inherited small RNAs in the germline.

One-Sentence Summary

Pseudouridine marks germline small RNAs in plants and mammals, impacting epigenetic inheritance via nuclear transport.
Multiple myeloma long-term survivors display sustained immune alterations decades after first line therapy
Authors: Lutz Raphael , Grünschläger Florian , Simon Malte , Bauer Marcus , Yousefian Schayan , Beumer Niklas , Jopp-Saile Lea , Awwad Mohamed H.S. , Steinbuss Georg , Sedlmeier Anastasia , Boch Tobias , Vonficht Dominik , Baertsch Marc-Andrea , Durie Brian G.M. , Weinhold Niels , Raab Marc S. , Wickenhauser Claudia , Trumpp Andreas , Müller-Tidow Carsten , Hübschmann Daniel , Brors Benedikt , Goldschmidt Hartmut , Imbusch Charles D. , Hundemer Michael , Haas Simon
Published: May 2023

The long-term consequences of cancer or cancer therapy on the patients’ immune system years after cancer-free survival remain poorly understood. Here, we have performed an in-depth characterization of the bone marrow ecosystem of multiple myeloma long-term survivors at initial diagnosis and up to 17 years following cancer-free survival. Using comparative single-cell analyses in combination with molecular, genomic and functional approaches, we demonstrate that multiple myeloma long-term survivors display pronounced alterations in their bone marrow microenvironment associated with impaired immunity. These immunological alterations were frequently driven by an inflammatory immune circuit fueled by the long-term persistence or resurgence of residual myeloma cells. Notably, even in the complete absence of any detectable residual disease for decades, sustained changes in the immune system were observed, suggesting an irreversible ‘immunological scarring’ caused by the initial exposure to the cancer and therapy. Collectively, our study provides key insights into the molecular and cellular bone marrow ecosystem of multiple myeloma long-term survivors, revealing reversible and irreversible alterations of the immune compartment, which can serve as diagnostic and predictive tools.

Statement of significance

Large-scale single-cell profiling of a unique cohort of multiple myeloma long-term survivors uncovered that exposure to cancer and its treatment causes both reversible and irreversible immune alterations associated with impaired immunity. These findings have far-reaching implications for the understanding of long-term immune alterations in cancer, which need to be considered also in the context of immune therapeutic approaches. Furthermore, our study demonstrates how cancer-associated immune trafficking can be used to predict disease re-initiation in the bone marrow, opening new avenues for minimally invasive disease monitoring.
autoStreamTree: Genomic variant data fitted to geospatial networks
Authors: Chafin Tyler K. , Mussmann Steven M. , Douglas Marlis R. , Douglas Michael E.
Published: May 2023

Landscape genetics is a statistical framework that parses genetic variation within the context of spatial covariates, but current analytical methods typically fail to accommodate the unique topologies and autocorrelations inherent to network-configured habitats (e.g., streams or rivers). autoStreamTree analyzes and visualizes genome-wide variation across dendritic networks (i.e., riverscapes).

Availability and Implementation

autoStreamTree is an open source workflow (https://github.com/tkchafin/autostreamtree) that automatically extracts a minimal graph representation of a geospatial network from a provided shapefile, then ‘fits’ the components of genetic variation using a least-squares algorithm. To facilitate downstream population genomic analyses, genomic variation can be represented per-locus, per-SNP, or via microhaplotypes (i.e., phased data). We demonstrate the workflow by quantifying genetic variation in Speckled Dace (Rhinichthys osculus)versusenvironmental covariates, with putative adaptive variants subsequently identified.

Contact

tyler.chafin@bioss.ac.uk