bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe acute respiratory syndrome coronavirus 2 infection altered the factors associated with headache: evidence from a multicenter community-based case–control study
Authors: Ali Mohammad
Published: December 2022

Introduction:

Headache is one of the significant global public health concerns. Furthermore, it is a standard feature of patients with acute and postacute COVID-19.

Objectives:

This study aimed to estimate and compare the prevalence of headaches among postacute COVID and non-COVID individuals and identify and contrast the risk factors between both groups.

Methods:

This was a multicenter case–control study. Individuals who had recovered from acute SARS-CoV-2 infection were considered “case”, and those who never tested positive for COVID-19 were considered “control.” Headaches were measured using the musculoskeletal subscale of the subjective health complaints scale. Multiple logistic regression analysis was used to identify the predictors of headaches.

Results:

A total of 878 individuals (439 cases) aged 38.30 ± 12.77 years (mean ± standard deviation) participated in this study. The prevalence of headaches was 26.2% among COVID-19 survivors; however, only 10.7% of unaffected participants reported headaches at the same time. Regression analyses suggested that the recovery duration from acute COVID-19 ≤ 90 days (adjusted odds ratio [AOR] = 2.03, CI = 1.13–3.65) was the only predictor of headache among postacute COVID-19 survivors. However, the female gender (AOR = 3.09, 95% CI = 1.51–6.32), members of a joint family (AOR = 1.99, 95% CI = 1.02–3.90), and city dwellers (AOR = 2.43, 95% CI = 0.94–6.25) were the predictor of headache among non-COVID participants.

Conclusion:

This study found a higher prevalence of headaches among COVID-19 survivors. In addition, predictors of headache among cases and controls were unmatched, indicating heterogenous impact of COVID-19 on human health. The health care providers should be informed of the study's results when discussing better practices to mitigate the burden of headaches.
Vascular Safe Zones for Facial Soft Tissue Filler Injections
Authors: Cotofana Sebastian , Lowrey Nicola , Frank Konstantin , Ziebart Rachel , Guertler Anne , Freytag Lysander , Helm Sabrina , Alfertshofer Michael G. , Moellhoff Nicholas
Published: December 2022

The number of soft tissue filler injections performed by aesthetic injectors has continued to increase over the last few years. To provide a high standard of safety and achieve individualized, reproducible, and long-lasting outcomes, aesthetic injectors must have a solid foundation in anatomy, facial biomechanics, rheology, and injection biomechanics. Adverse events associated with soft tissue filler injections can be severe, especially if the aesthetic injector unintentionally injects the soft tissue filler into the patient's arterial vascular circulation and the administered product reaches the arterial bloodstream. Although the face has a rich arterial vascular supply that may seem overwhelmingly complex, it can be broken down systematically according to its internal and external vascular territories. To provide guidance for aesthetic practitioners performing minimally invasive facial injections for aesthetic purposes, this narrative article will discuss the course, depth, and branching pattern of the facial arteries based on the most frequently injected anatomical regions. In this article, we focus on vascular safe zones rather than danger zones.
Impact of short message service and peer navigation on linkage to care and antiretroviral therapy initiation in South Africa
Authors: Lippman Sheri A. , de Kadt Julia , Ratlhagana Mary J. , Agnew Emily , Gilmore Hailey , Sumitani Jeri , Grignon Jessica , Gutin Sarah A. , Shade Starley B. , Gilvydis Jennifer M. , Tumbo John , Barnhart Scott , Steward Wayne T.
Published: December 2022

Objective:

We examine the efficacy of short message service (SMS) and SMS with peer navigation (SMS + PN) in improving linkage to HIV care and initiation of antiretroviral therapy (ART).

Design:

I-Care was a cluster randomized trial conducted in primary care facilities in North West Province, South Africa. The primary study outcome was retention in HIV care; this analysis includes secondary outcomes: linkage to care and ART initiation.

Methods:

Eighteen primary care clinics were randomized to automated SMS (n = 7), automated and tailored SMS + PN (n = 7), or standard of care (SOC; n = 4). Recently HIV diagnosed adults (n = 752) were recruited from October 2014 to April 2015. Those not previously linked to care (n = 352) contributed data to this analysis. Data extracted from clinical records were used to assess the days that elapsed between diagnosis and linkage to care and ART initiation. Cox proportional hazards models and generalized estimating equations were employed to compare outcomes between trial arms, overall and stratified by sex and pregnancy status.

Results:

Overall, SMS (n = 132) and SMS + PN (n = 133) participants linked at 1.28 [95% confidence interval (CI): 1.01–1.61] and 1.60 (95% CI: 1.29–1.99) times the rate of SOC participants (n = 87), respectively. SMS + PN significantly improved time to ART initiation among non-pregnant women (hazards ratio: 1.68; 95% CI: 1.25–2.25) and men (hazards ratio: 1.83; 95% CI: 1.03–3.26) as compared with SOC.

Conclusion:

Results suggest SMS and peer navigation services significantly reduce time to linkage to HIV care in sub-Saharan Africa and that SMS + PN reduced time to ART initiation among men and non-pregnant women. Both should be considered candidates for integration into national programs.

Trial registration:

NCT02417233, registered 12 December 2014; closed to accrual 17 April 2015.
68Ga-FAPI-04 PET/CT Versus 18F-FDG PET/CT in the Detection of Malignant Gastrointestinal Stromal Tumor
Authors: Zhang Zeyu , Jiang Hongyuan , Zhang Lu , Cheng Chao , Zuo Changjing
Published: December 2022

A 65-year-old man presented with abdominal bloating for approximately 4 weeks. After CT imaging, it was diagnosed as gastric carcinoma with hepatic metastasis. 68Ga-FAPI-04 PET/CT revealed much higher tumor-to-background contrast and more metastatic lesions compared with 18F-FDG PET/CT in this case. Following gastroscopy and pathological examination, the final diagnosis was malignant gastrointestinal stromal tumor. This case demonstrated that 68Ga-FAPI-04 PET/CT was more sensitive than 18F-FDG PET/CT for detecting primary and metastatic lesions in malignant gastrointestinal stromal tumor.
A Tale of 3 Tracers
Authors: Lawal Ismaheel O. , Adediran Omotayo Atinuke , Muzahir Saima , Friend Sarah , Bhave Manali Ajay , Meisel Jane , Torres Mylin A. , Styblo Toncred Marya , Graham Cathy , Holbrook Anna , Kalinsky Kevin , Fielder Bridget , Crowe Ronald J. , Ulaner Gary A. , Schuster David M.
Published: December 2022

A 41-year-old woman with invasive lobular carcinoma of the breast underwent sequential 68Ga-PSMA-11 PET/CT and 18F-fluciclovine PET/CT as part of an ongoing clinical trial (NCT04750473). 68Ga-PSMA PET/CT showed increased radiotracer uptake in the uterine endometrium and left adnexa. 18F-fluciclovine PET/CT showed increased radiotracer uptake in a leiomyomatous uterus. A clinical 18F-FDG PET/CT demonstrated radiotracer uptake in the endometrium and a circumferential area of uptake in the left adnexa, a pattern more similar to the 68Ga-PSMA uptake pattern. This case highlights the discordance in the uptake pattern of 2 radiotracers approved for prostate cancer imaging but increasingly used in non-prostate malignancies imaging.
Increased 68Ga-FAPI Uptake in Psammomatous Meningioma in a Patient With Gallbladder Cancer
Authors: Peng Dengsai , Yang Xiao , Yan Qin , Gong Weidong , Chen Yue
Published: December 2022

A 70-year-old woman with a gallbladder mass was enrolled in our clinical trial of 68Ga-FAPI PET/CT study in tumors. Increased tracer uptake was noted in the gallbladder. In addition, focal uptake was localized in a lesion beside the falx cerebri. According to the location and radiological and clinical characteristics, a diagnosis of meningioma was made.
Isolated Urinary Bladder Metastasis in Renal Cell Carcinoma Detected on 18F-FDG PET/CT Scan
Authors: Dey Sudip , Sunil Gadde Sathya , Verma Ritu , Belho Ethel Shangne , Drolia Babita , Jain Sunila , Gupta Nitin
Published: December 2022

Renal cell carcinoma (RCC) is an aggressive carcinoma with hematogenous spread commonly to lungs, liver, and bones. However, few cases of isolated urinary bladder metastasis have also been reported. Here we report a case of 63-year-old man, a known case of left RCC (clear cell type), post left nephrectomy, who was on regular clinicoradiological follow-up. He presented with complaints of painless hematuria; on further evaluation, 18F-FDG PET/CT revealed few FDG-avid intramural nodular lesions along the walls of urinary bladder. He underwent TURBT, and the tissue was sent for histopathological examination, which was diagnostic of metastatic RCC.
Standardized Intraoperative Neuromonitoring Procedure is Feasible in Transoral Endoscopic Thyroidectomy
Authors: Oh Moon Young , Lee Min Jung , Lee Jung-Man , Chai Young Jun
Published: December 2022

Background:

Intraoperative neuromonitoring in thyroid surgeries has become popular, but the standardized manner of intraoperative neuromonitoring during transoral endoscopic thyroidectomy vestibular approach (TOETVA) is not well established. This study evaluated the feasibility of using a standardized intraoperative neuromonitoring method for TOETVA.

Methods:

Medical records of consecutive patients who underwent TOETVA with intraoperative neuromonitoring were retrospectively reviewed. Patients were positioned before intubation to prevent tube migration, then intubated using video laryngoscopy. The electromyography amplitudes of the vagal nerves and the recurrent laryngeal nerves were checked before (V1, R1) and after (V2, R2) thyroid resection. V1 and V2 signals were evaluated using a long ball tip stimulator with a stimulus current of 3 mA. R1 and R2 signals were obtained using the stimulus current of 1 to 3 mA.

Results:

Forty-two patients (3 males and 39 females) were included. Lobectomy was performed in 40 patients (95.2%) and total thyroidectomy in 2 (4.8%). Pathologic diagnoses were 30 papillary thyroid carcinomas, 2 follicular thyroid carcinomas, and 9 benign diseases. Conversion to open surgery occurred in 1 patient due to bleeding. Thus, 43 nerves at risk in 41 patients were analyzed. V1 and R1 signals were detected from all nerves. The mean V1 and R1 amplitudes were 738.7±391.4 μV and 804.4±347.5 μV, respectively, and 38 (88.3%) and 39 (90.7%) nerves had R1 and V1 amplitudes of more than 500 μV. There were 2 cases (4.6%) of transient recurrent laryngeal nerve injury. R2 and V2 signals were detected in the 41 remaining nerves. The mean R2 and V2 amplitudes were 917.2±505.2 μV and 715.7±356.2 μV, respectively, and 36 (87.8%) and 32 (78.0%) nerves had respective R2 and V2 amplitudes of more than 500 μV.

Conclusions:

Intraoperative neuromonitoring could be performed in a standardized manner in TOETVA, and the quality of intraoperative neuromonitoring was excellent. Further studies are needed to verify the feasibility of the current approach.
Is There a Relationship Between Helicobacter Pylori and GERD Before Laparoscopic Sleeve Gastrectomy?
Authors: Şen Ozan , Oray Şeref , Gökhan Türkçapar Ahmet
Published: December 2022

Aim:

The aim of this study is to determine the prevalence of Helicobacter pylori (HP) in patients before laparoscopic sleeve gastrectomy (LSG) and to reveal whether HP is associated with gastroesophageal reflux disease (GERD) before LSG.

Methods:

The study included 435 patients who underwent primary LSG between April 2018 and September 2021. All patients underwent preoperative endoscopy. All patients were investigated for the presence of HP. No treatment for HP eradication was given to any of the patients. Patients were divided into 2 groups HP (+) and HP(-), and compared for GERD, complications, and weight loss before and after LSG.

Results:

The mean age of the patients was 38.3±11 years (56.1% female), and the mean BMI was 44.2±7.1 kg/m2. Symptomatic GERD was found in 102 (23.4%) patients. Endoscopy showed hiatal hernia in 42 (9.7%) patients, and these patients also underwent hiatal hernia repair in the same session. HP was (+) in 125 (28.7%) patients. HP (+) patients were assigned to Group A, while HP (-) patients were assigned to Group B. In the preoperative period, the rate of symptomatic GERD was 22.4% (n=28/125) in Group A and 23.9% (n=74/310) in Group B (P=0.74). The mean follow-up period was 17±5.7 (range, 12 to 28) months. The mean BMI decreased to 28.3±4.9 kg/m2 at 12 months after LSG. Given the association between HP and GERD after LSG, it was 25.6% (n=32/125) in Group A and 20% (n=62/310) in Group B (P=0.2). In addition, there was no difference between the 2 groups in terms of weight loss.

Conclusion:

This study showed no difference between patients with or without HP infection in terms of GERD before LSG.
Trajectory phase transitions in non-interacting systems: all-to-all dynamics and the random energy model
Authors: Garrahan Juan P. , Manai Chokri , Warzel Simone
Published: December 2022

We study the fluctuations of time-additive random observables in the stochastic dynamics of a system of

N

non-interacting Ising spins. We mainly consider the case of all-to-all dynamics where transitions are possible between any two spin configurations with uniform rates. We show that the cumulant generating function of the time-integral of a normally distributed quenched random function of configurations, i.e. the energy function of the random energy model (REM), has a phase transition in the large

N

limit for trajectories of any time extent. We prove this by determining the exact limit of the scaled cumulant generating function. This is accomplished by connecting the dynamical problem to a spectral analysis of the all-to-all quantum REM. We also discuss finite

N

corrections as observed in numerical simulations.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
Quantum annealing: an overview
Authors: Rajak Atanu , Suzuki Sei , Dutta Amit , Chakrabarti Bikas K.
Published: December 2022

In this review, after providing the basic physical concept behind quantum annealing (or adiabatic quantum computation), we present an overview of some recent theoretical as well as experimental developments pointing to the issues which are still debated. With a brief discussion on the fundamental ideas of continuous and discontinuous quantum phase transitions, we discuss the Kibble–Zurek scaling of defect generation following a ramping of a quantum many body system across a quantum critical point. In the process, we discuss associated models, both pure and disordered, and shed light on implementations and some recent applications of the quantum annealing protocols. Furthermore, we discuss the effect of environmental coupling on quantum annealing. Some possible ways to speed up the annealing protocol in closed systems are elaborated upon: we especially focus on the recipes to avoid discontinuous quantum phase transitions occurring in some models where energy gaps vanish exponentially with the system size.

This article is part of the theme issue ‘Quantum annealing and computation: challenges and perspectives’.
MRSA in the bursa: an unusual complication of MRSA bacteremia causing bilateral acromioclavicular septic arthritis
Authors: Rodriguez-Quick Victoria A. , Llop Alexander , Dimas Kevin , Girgawy Essam A.
Published: December 2022

Background. Bacteraemia is known to cause serious complications including metastatic infections such as infective endocarditis, vertebral osteomyelitis, iliopsosas abscesses and septic arthritis. Bilateral septic arthritis, however, is a rare medical emergency with limited previous reports.

Staphylococcus

species are the most common organisms identified as a result of suspected haematogenous spread from bacteraemia, direct inoculation or translocation from adjacent tissues. While unilateral septic arthritis due to intravenous drug use is a common phenomenon warranting prompt treatment to preserve mobility, function and quality of life, cases of bilateral infections are exceedingly rare. Furthermore, infections involving the acromioclavicular joint are not commonly documented in the literature.

Case Presentation. We present a case of a 41-year-old female with a history of intravenous drug use who presented with low back pain and was found to have methicillin-resistant

Staphylococcus aureus

bacteraemia that was complicated with metastatic infections causing bilateral acromioclavicular joint septic arthritis.

Conclusions. Metastatic infections from bacteraemia are serious complications that can lead to septic arthritis. Though septic arthritis is best known in previous case reports to present as a unilateral infection, rare cases of bilateral involvement warrant further consideration. A thorough history and physical examination evaluating all joints can identify such atypical presentations. Septic arthritis remains a medical emergency, and it is imperative that clinicians recognize unusual presentations to avoid delays in treatment that can lead to detrimental impacts to quality of life.
Tethering by Uso1 is dispensable: The Uso1 monomeric globular head domain interacts with SNAREs to maintain viability
Authors: Bravo-Plaza Ignacio , Tagua Víctor G. , Arst Herbert N. , Alonso Ana , Pinar Mario , Monterroso Begoña , Galindo Antonio , Peñalva Miguel Á.
Published: December 2022

Uso1/p115 and RAB1 tether ER-derived vesicles to the Golgi. Uso1/p115 contains a globular-head-domain (GHD), a coiled-coil (CC) mediating dimerization/tethering and a C-terminal region (CTR) interacting with golgins. Uso1/p115 is recruited to vesicles by RAB1. Paradoxically, genetic studies placed Uso1 acting upstream of, or in conjunction with RAB1 (Sapperstein et al., 1996). We selected two missense mutations inuso1resulting in E6K and G540S substitutions in the GHD permitting growth of otherwise inviablerab1-deficientAspergillus nidulans.Remarkably, the double mutant suppresses the complete absence of RAB1. Full-length Uso1 and CTRΔ proteins are dimeric and the GHD lacking the CC/CTR is monomeric irrespective of whether they carry or not E6K/G540S. Microscopy showed recurrence of Uso1 on puncta (60 sec half-life) colocalizing with RAB1 and less so with early Golgi markers Sed5 and GeaA/Gea1/Gea2. Localization of Uso1 but not of Uso1E6K/G540Sto puncta is abolished by compromising RAB1 function, indicating that E6K/G540S creates interactions bypassing RAB1. By S-tag-coprecipitation we demonstrate that Uso1 is an associate of the Sed5/Bos1/Bet1/Sec22 SNARE complex zippering vesicles with the Golgi, with Uso1E6K/G540Sshowing stronger association. Bos1 and Bet1 bind the Uso1 GHD directly, but Bet1 is a strong E6K/G540S-independent binder, whereas Bos1 is weaker but becomes as strong as Bet1 when the GHD carries E6K/G540S. AlphaFold2 predicts that G540S actually increases binding of GHD to the Bos1 Habc domain. In contrast, E6K seemingly increases membrane targeting of an N-terminal amphipathicα-helix, explaining phenotypic additivity. Overexpression of E6K/G540S and wild-type GHD complementeduso1Δ. Thus, a GHD monomer provides the essential Uso1 functions, demonstrating that long-range tethering activity is dispensable. Therefore, when enhanced by E6K/G540S, Uso1 binding to Bos1/Bet1 required to regulate SNAREs bypasses both the contribution of RAB1 to Uso1 recruitment and the reported role of RAB1 in SNARE complex formation (Lupashin and Waters, 1997), suggesting that the latter is consequence of the former.
SARS-CoV-2 infection- induced seroprevalence among children and associated risk factors during pre- and omicron-dominant wave, from January 2021 through November 2022, Thailand: Longitudinal study
Authors: Suntronwong Nungruthai , Vichaiwattana Preeyaporn , Klinfueng Sirapa , Puenpa Jiratchaya , Kanokudom Sitthichai , Assawakosri Suvichada , Chansaenroj Jira , Srimuan Donchida , Thatsanatorn Thaksaporn , Songtaisarana Siriporn , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Poovorawan Yong
Published: December 2022

Background

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic in young children. Therefore, the true rate of infection is likely underestimated. Few data are available on the rate of infections in young children, and studies on the SARS-CoV-2 seroprevalence among children during omicron wave are limited. Our study aims to assess the SARS-CoV-2 infection-induced seroprevalence among children and estimated the associated risk factors for seropositivity.

Methods

A longitudinal serological survey was conducted from January 2021 through November 2022. Samples were tested for anti-nucleocapsid (N) IgG, anti-receptor binding domain (RBD) IgG using a chemiluminescent microparticle immunoassay (CMIA) and detected anti-RBD Immunoglobulin (Ig) using an electrochemiluminescence immunoassay (ECLIA). The vaccination and SARS-CoV-2 infection history were collected.

Results

A total of 452 serum samples were obtained from 249 children aged 5–7 years old who were annually followed-up in the longitudinal serological survey. Of these, 191 participants provided samples at two serial time points, including during the pre-and omicron dominant wave. Overall, seroprevalence induced by SARS-CoV-2 infection was increased from 9.1% (95%CI: 0.6-12.6%) during the pre-omicron wave to 49.7% (95%CI: 35.9-66.8%) during the omicron wave. Amongst seropositive individuals, the infection-induced seroprevalence was lower in vaccinated participants than those with no vaccination (40.4% vs. 57.4%; risk ratio, 0.71; 95%CI: 0.52–0.95). Nevertheless, the ratio of seropositive cases per recalled infection was 1.56 during the omicron dominant wave. In addition, overall seroprevalence induced by infection, vaccination and hybrid immunity was 76.6% (151/197; 95%CI: 54.6-97.9%) between January and November 2022.

Conclusions

our study reports an increase in infection-induced seroprevalence among children during the omicron wave. These findings highlight that estimating seroprevalence is crucial to monitor SARS-CoV-2 exposure, particularly in asymptomatic infection, and help to optimize public health policies and determine the effect of immunization in the pediatric population.
Profile of patients treated with intravitreal anti-vascular endothelial growth factor injections in Bhutan: a 3-year national survey
Authors: Rai Bhim B. , Rai Deepa , Maddess Ted
Published: December 2022

Purpose

Ocular vascular diseases are common causes of visual impairment and blindness, for which intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections in Bhutan. This is the first study of its kind to inform the national health policy.

Methods

For this retrospective study, we reviewed the surgical registers of the vitreoretinal unit across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for intravitreal anti-VEGF injections were logged. A descriptive analysis was performed.

Results

A total of 381 patients received intravitreal anti-VEGF injections in the operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%). The mean age was 65.2 ± 13.5 years, ranging from 13 to 90 years, and a median of 69 years. Majority of the treated eyes (117, 30.7%) had BCVA <3/60 to light perception (PL), and another 51 eyes (13.4%) had < 6/60 to 3/60. The most common indication for anti-VEGF injection was neovascular AMD (168 cases, 42.2%), followed by retinal vein occlusion (132 cases, 34.6%), diabetic macular oedema and retinopathy (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%).

Conclusions

Bhutan faces both economic and geographic challenges, on top of limited human resources for managing vitreoretinal diseases. With an ever-increasing load of vitreoretinal diseases, and systemic diseases like diabetes and hypertension, there is a need to improve vitreoretinal services. Regular vitreoretinal services are provided only at the national referral hospital located in the north-west. For successful management, an effective community screening program, right referrals, and proper transport facilities must go hand-in-hand, and or extend regular vitreoretinal services to regional referral hospitals.
A non-canonical sensing pathway mediatesPlasmodiumadaptation to AA deficiency
Authors: Marreiros Inês M. , Marques Sofia , Parreira Ana , Mastrodomenico Vincent , Mounce Bryan C. , Harris Chantal T. , Kafsack Björn F. , Billker Oliver , Zuzarte-Luís Vanessa , Mota Maria M.
Published: December 2022

Eukaryotes have canonical pathways for responding to amino acid (AA) availability. Under AA-limiting conditions, the TOR complex is repressed, whereas the sensor kinase GCN2 is activated. While these pathways have been highly conserved throughout evolution, malaria parasites are a rare exception. Despite auxotrophic for most AA,Plasmodiumdoes not have either a TOR complex nor the GCN2-downstream transcription factors. While Ile starvation has been shown to trigger eIF2α phosphorylation and a hibernatory-like response, the overall mechanisms mediating detection and response to AA fluctuation in the absence of such pathways has remained elusive. Here we show thatPlasmodiumparasites rely on an efficient sensing pathway to respond to AA fluctuations. A phenotypic screen of kinase knockout mutant parasites identified nek4, eIK1 and eIK2 – the last two clustering with the eukaryotic eIF2α kinases - as critical forPlasmodiumto sense and respond to distinct AA-limiting conditions. Such AA-sensing pathway is temporally regulated by these kinases at distinct life cycle stages and allows parasites to actively fine-tune replication and development in response to AA availability. Collectively, our data identify a previously unknown set of heterogeneous responses to AA depletion, mediated by a complex mechanism that is critical for modulating parasite cell cycle and survival.
TurboID reveals the proxiomes of CGE1, VIPP1, and VIPP2 inChlamydomonas reinhardtii
Authors: Kreis Elena , König Katharina , Sommer Frederik , Schroda Michael
Published: December 2022

InChlamydomonas reinhardtii, VIPP1 and VIPP2 play a role in the sensing and coping with membrane stress and in thylakoid membrane biogenesis. To gain more insight into these processes, we aimed to identify proteins interacting with VIPP1/2 in the chloroplast and chose proximity labeling (PL) for this purpose. We used the transient interaction between the nucleotide exchange factor CGE1 and stromal HSP70B as test system. While PL with APEX2 and BioID proved to be inefficient, TurboID resulted in significant biotinylationin vivo. TurboID-mediated PL with VIPP1/2 as baits under ambient and H2O2stress conditions confirmed known interactions of VIPP1 with VIPP2, HSP70B and CDJ2. Novel proteins in the VIPP1/2 interaction network can be grouped into proteins involved in the biogenesis of thylakoid membrane complexes and the regulation of photosynthetic electron transport. A third group comprises 11 proteins of unknown function whose genes are upregulated under chloroplast stress conditions. We named them VIPP PROXIMITY LABELING (VPL1-11). and confirmed the proximity of VIPP1 and VPL2 in a reciprocal experiment. Our results demonstrate the robustness of TurboID-mediated PL for studying protein interaction networks in the chloroplast ofChlamydomonasand pave the way for analyzing functions of VIPPs in thylakoid biogenesis and stress responses.
Targeted chromosomal barcoding establishes direct genotype-phenotype associations for antibiotic resistance inMycobacterium abscessus
Authors: Calvet-Seral Juan , Crespo-Yuste Estefanía , Mathys Vanessa , Rodriguez-Villalobos Hector , Ceyssens Pieter-Jan , Martin Anandi , Gonzalo-Asensio Jesús
Published: December 2022

A bedaquiline resistantMycobacterium abscessusisolate was sequenced and a candidate mutation in theatpEgene was identified as responsible for the antibiotic resistance phenotype. To establish a direct genotype-phenotype relationship of this D29A mutation, we developed a recombineering-based method consisting of the specific replacement of the desired mutation in the bacterial chromosome. As surrogate bacteria, we used twoM. abscessusantibiotic susceptible strains: ATCC19977, and the SL541 clinical isolate. The allelic exchange substrates used in recombineering carried either the sole D29A mutation, or a genetic barcode of silent mutations in codons flanking the D29A mutation. After selection of bedaquiline resistantM. abscessuscolonies, transformed with both substrates, we obtained equivalent numbers of recombinants. These resistant colonies were analyzed by allele-specific PCR, and Sanger sequencing, demonstrating that the presence of the genetic barcode is linked to the targeted incorporation of the desired mutation in its chromosomal location. All recombinants displayed the same minimal inhibitory concentration to bedaquiline than the original isolate, from which the D29A mutation was identified. Finally, to demonstrate the broad applicability of this method, we confirmed the association of bedaquiline resistance with theatpEA64P mutation, performed in independentM. abscessusstrains and by independent researchers.
Characterisation of neonatalStaphylococcus capitisNRCS-A isolates compared with non NRCS-AStaphylococcus capitisfrom neonates and adults
Authors: Felgate Heather , Sethi Dheeraj , Faust Kirstin , Kiy Cemsid , Härtel Christoph , Rupp Jan , Clifford Rebecca , Dean Rachel , Tremlett Catherine , Wain John , Langridge Gemma , Clarke Paul , Page Andrew , Webber Mark A
Published: December 2022

Staphylococcus capitisis a frequent cause of Late-Onset Sepsis (LOS) in neonates admitted to Neonatal Intensive Care Units (NICU). The NRCS-A clone ofS. capitishas been isolated from NICUs globally although the reasons for the global success of this clone are not understood.

We analysed a collection ofS. capitiscolonising babies admitted to two NICUs, one in the UK and one in Germany as well as corresponding pathological clinical isolates. Genome analysis identified 3 groups; non-NRCS-A isolates, NRCS-A isolates, and a group of ‘proto NRCS-A’ - isolates closely related to NRCS-A but not associated with neonatal infection. All bloodstream isolates belonged to the NRCS-A group and were indistinguishable from strains carried on the skin or in the gut. NRCS-A isolates showed increased tolerance to chlorhexidine and antibiotics relative to the otherS. capitisas well as enhanced ability to grow at higher pH values. Analysis of 138 pangenomes of the clades identified characteristicnsrandtarJgenes in the NRCS-A and proto groups with a CRISPR-cas system only seen in NRCS-A isolates which also showed enrichment of genes for metal acquisition and transport.

We found evidence for transmission ofS. capitisNRCS-A within NICU, with related isolates shared between babies and multiple acquisitions by some babies. Our data show NRCS-A strains commonly colonise uninfected babies in NICU representing a potential reservoir for potential infection. This work provides more evidence that adaptation to survive in the gut and on skin facilitates spread of NRCS-A, and that metal acquisition and tolerance may be important to the biology of NRCS-A. Understanding how NRCS-A survives in NICUs can help develop infection control procedures against this clone.
Scavenger receptor endocytosis controls apical membrane morphogenesis in theDrosophilaairways
Authors: Pinheiro Ana S. , Tsarouhas Vasilios , Senti Kirsten , Arefin Badrul , Samakovlis Christos
Published: December 2022

The acquisition of distinct branch sizes and shapes is a central aspect in tubular organ morphogenesis and function. In theDrosophilaairway tree, the interplay of apical ECM components with the underlying membrane and cytoskeleton controls tube elongation, but the link between ECM composition with apical membrane morphogenesis and tube size regulation is elusive. Here, we characterized Emp (epithelial membrane protein), aDrosophilaCD36-homologue belonging to the scavenger receptor class B protein-family.empmutant embryos fail to internalize the luminal chitin deacetylases Serp and Verm at the final stages of airway maturation and die at hatching with liquid filled airways. Emp localizes in apical epithelial membranes and shows cargo selectivity for LDLr-domain containing proteins.empmutants also display over elongated tracheal tubes with increased levels of the apical proteins Crb, DE-cad and phosphorylated Src (p-Src). We show that Emp associates and organizes the βH-Spectrin cytoskeleton and is itself confined by apical F-actin bundles. Overexpression or loss of its cargo protein Serp lead to abnormal apical accumulations of Emp and perturbations in p-Src levels. We propose that during morphogenesis, Emp senses and responds to luminal cargo levels by initiating apical membrane endocytosis along the longitudinal tube axis and thereby restricts airway elongation.
Point-of-care peptide hormone production enabled by cell-free protein synthesis
Authors: DeWinter Madison A. , Thames Ariel Helms , Guerrero Laura , Kightlinger Weston , Karim Ashty S. , Jewett Michael C.
Published: December 2022

In resource-limited settings, it can be difficult to safely deliver sensitive biologic medicines to patients due to cold chain and infrastructure constraints. Point-of-care drug manufacturing could circumvent these challenges since medicines could be produced locally and used on-demand. Towards this vision, we combine cell-free protein synthesis (CFPS) and a 2-in-1 affinity purification and enzymatic cleavage scheme to develop a platform for point-of-care drug manufacturing. As a model, we use this platform to synthesize a panel of peptide hormones, an important class of medications that can be used to treat a wide variety of diseases including diabetes, osteoporosis, and growth disorders. With this approach, temperature-stable lyophilized CFPS reaction components can be rehydrated with DNA encoding a SUMOylated peptide hormone of interest when needed. Strep-Tactin®affinity purification and on-bead SUMO protease cleavage yields peptide hormones in their native form that are recognized by ELISA antibodies and that can bind their respective receptors. With further development to ensure proper biologic activity and patient safety, we envision this platform could be used to manufacture valuable peptide hormone drugs at the point-of-care in resource-limited settings.
Application of self-organizing maps to AFM-based viscoelastic characterization of breast cancer cell mechanics
Authors: Weber Andreas , Vivanco Maria dM. , Toca-Herrera José L.
Published: December 2022

Cell mechanical properties have been proposed as label free markers for diagnostic purposes in diseases such as cancer. Cancer cells show altered mechanical phenotypes compared to their healthy counterparts. Atomic Force Microscopy (AFM) is a widely utilized tool to study cell mechanics. These measurements often need skilful users, physical modelling of mechanical properties and expertise in data interpretation. Together with the need to perform many measurements for statistical significance and to probe wide enough areas in tissue structures, the application of machine learning and artificial neural network techniques to automatically classify AFM datasets has received interest recently. We propose the use of self-organizing maps (SOMs) as unsupervised artificial neural network applied to mechanical measurements performed via AFM on epithelial breast cancer cells treated with different substances that affect estrogen receptor signalling. We show changes in mechanical properties due to treatments, as estrogen softened the cells, while resveratrol led to an increase in cell stiffness and viscosity. These data were then used as input for SOMs. Our approach was able to distinguish between estrogen treated, control and resveratrol treated cells in an unsupervised manner. In addition, the maps enabled investigation of the relationship of the input variables.
Sexually Transmitted Infections among Key Populations in India: A Protocol for Systematic Review
Authors: Bhatta Mihir , Majumdar Agniva , Ghosh Utsha , Ghosh Piyali , Banerji Papiya , Aridoss Santhakumar , Royal Abhiske , Biswas Subrata , Venkatesh Bhumika Tumkur , Adhikary Rajatsuvra , Dutta Shanta
Published: December 2022

Background

Sexually transmitted infections (STIs) are one of the leading causes of health, and economic burdens in the developing world, leading to considerable morbidity, mortality, and stigma. The incidence and prevalence of the four curable STIs viz syphilis, gonorrhoea, chlamydia, and trichomoniasis vary remarkably across different geographical locations. In India, the prevalence of four curable STI among general populations is in between 0 to 3.9 per cent. However, it is assumed that STI prevalence is much higher among subpopulations practicing high-risk behaviour. Like men who have sex with men (MSM), transgender (TG), injecting drug users (IDU) and female sex worker (FSW).

Objectives

In the present circumstances, a systematic review is necessary to integrate the available data from previously published peer-reviewed articles and published reports from several competent authorities to provide the prevalence and geographical distribution of the four curable STIs among the key population of India.

Methods

All available articles will be retrieved from PubMed, Google Scholar, Cochrane database, Scopus, Science Direct, and the Global Health network using the appropriate search terms. The data will be extracted through data extraction form as per PICOS (population, intervention, comparison, outcome, study design) framework. Risk of bias and quality assessment will be performed with the help of the Funnel plot and Newcastle - Ottawa Quality Assessment Scale.

Conclusion

The future systematic review, which will be generated from the present protocol, may provide evidence of the prevalence and geographical distribution of the four curable STIs among the key population of India. The findings of the future systematic review will strengthen the existing surveillance system in India, to determine the above-mention STIs prevalence among key populations in India.

Protocol registration number

International Prospective Register for Systematic Reviews (PROSPERO) number CRD42022346470
Psychosocial attributes of housing and their relationship with health among refugee and asylum-seeking populations in high-income countries: systematic review
Authors: Brake Tessa , Dudek Verena , Sauzet Odile , Razum Oliver
Published: December 2022

Introduction

Housing as a social determinant of health should provide not only shelter, but also a feeling of home. We explored psychosocial pathways creating a sense of home and influencing the relationship between housing and health among asylum seekers and refugees (ASR) in high-income countries.

Methods

We performed a systematic review. To be included, studies had to be peer-reviewed, published between 1995 and 2022, and focus on housing and health of ASR in high-income countries. We conducted a narrative synthesis.

Results

32 studies met the inclusion criteria. The psychosocial attributes influencing health most often identified werecontrol, followed byexpressing status, satisfaction, anddemand. Most attributes overlap with material/physical attributes and have an impact on ASR’s mental health. They are closely interconnected with each other.

Conclusions

Psychosocial attributes of housing play an important role in the health of ASR; they are closely associated with material/physical attributes. Therefore, future research on housing and health of ASR should routinely examine psychosocial attributes, but always in association with physical attributes. The connections between these attributes are complex and need to be further explored.

PROSPERO registration number

CRD42021239495
The adherens junction proteins α-catenin, vinculin and VASP cooperate to promote actin assembly
Authors: Said Rayan , Wang Hong , Pernier Julien , Narassimprakash Hemalatha , Roméro Stéphane , Gautreau Alexis M. , Mège René-Marc , Le Clainche Christophe
Published: December 2022

The cohesion of tissues requires that cells establish cell-cell junctions. Cells contact each other by forming Arp2/3-dependent lamellipodia before they initiate the formation of cadherin-based adherens junctions (AJs). Maturing AJs then assemble actin under force though the formation of a mechanosensitive complex comprising the actin-binding proteins α-catenin, vinculin and VASP, which individually act on the nucleation, elongation and organisation of actin filaments in different ways. However, the activity of the ternary complex that these actin-regulatory proteins form has not been investigated due to the difficulty of assembling this complex in vitro in the absence of force. Here, we first designed mutants of these proteins that interact independently of force. We then studied their activity by combining actin polymerization kinetics in fluorescence spectroscopy with observation of single actin filaments in TIRF microscopy. Our results reveal how α-catenin, vinculin and VASP combine their activities in a complex to inhibit Arp2/3-mediated branching, stimulate the nucleation and elongation of linear actin filaments from profilin-actin and crosslink these filaments into bundles. These findings shed light on the molecular mechanisms by which actin regulators synergistically control the transition of actin architecture and dynamics that accompanies the formation and maturation of AJs.
Structural basis for substrate recruitment by AMBRA1 E3 ligase receptor
Authors: Liu Ming , Wang Yang , Teng Fei , Mai Xinyi , Wang Xi , Su Ming-Yuan , Stjepanovic Goran
Published: December 2022

AMBRA1 is a tumor suppressor protein that functions as a substrate receptor of the ubiquitin conjugation system as part of autophagy and cell-cycle regulatory network. The highly intrinsic disorder of AMBRA1 has so far precluded its structural determination. To solve this problem, we analyzed the domain organization and dynamics of AMBRA1 using hydrogen deuterium exchange mass spectrometry (HDX-MS). High deuterium uptake indicates that AMBRA1 is a dynamic and largely unstructured protein, and can be stabilized upon interaction with DDB1, the adaptor of the Cullin4A/B E3 ligase complex. Here we present the cryo-EM structure of AMBRA1 in complex with DDB1 at 3 Å resolution. The structure shows that parts of N- and C-terminal structural regions in AMBRA1 fold together into the highly dynamic WD40 domain, and reveals how DDB1 engages with AMBRA1 to create a binding scaffold for substrate recruitment. AMBRA1 uses its N-terminal helix-loop-helix and WD40 domain to bind the double-propeller fold of DDB1, whereas different regions target the specific cellular substrates for ubiquitination. We also demonstrate that DDB1 binding-defective AMBRA1 mutants prevent ubiquitination of the substrate Cyclin D1in vitroand decreased number of autophagosomes in the cells. Together, these results provide structural insights into AMBRA1-ubiquitin ligase complex and suggests a mechanism by which the AMBRA1 acts as a hub involved in various physiological processes.
Integrated proteomics reveals the landscape of autophagy degradation in human neurons and autophagy receptors regulating neuronal activity
Authors: Zhou Xiaoting , Lee You-Kyung , Li Xianting , Kim Henry , Sanchez-Priego Carlos , Han Xian , Tan Haiyan , Zhou Suiping , Fu Yingxue , Purtell Kerry , Wang Qian , Holstein Gay , Tang Beisha , Peng Junmin , Yang Nan , Yue Zhenyu
Published: December 2022

Autophagy is a catabolic and self-degradative process crucial for maintaining cellular homeostasis. Malfunctional autophagy is implicated in neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we reported a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and LC3-interactome uncovers a role of neuronal autophagy in targeting primarily endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) proteins, and cAMP-PKA pathway, for degradation. Tubular ER and specific SV proteins are significant autophagy cargos in the axons. Functional validation identified calumenin as an ER resident autophagy receptor and illuminated a role of autophagy in regulating PKA and neuronal activity through AKAP11-mediated degradation. Our study thus reveals the landscape of autophagy degradation in human neurons and offers molecular insight into mechanisms of neurological disorders linked to autophagy deficiency.

Highlight

Integrated proteomics reveals the landscape of autophagy degradation in human neurons

Autophagy clears tubular ER and selective ER and synaptic vesicle proteins in neurons

Calumenin is an ER resident autophagy receptor

Autophagy controls PKA pathway and neuronal activity through autophagy receptor AKAP11
Detecting and staging diabetic retinopathy in retinal images using multi-branch CNN
Authors: Kusakunniran Worapan , Karnjanapreechakorn Sarattha , Choopong Pitipol , Siriapisith Thanongchai , Tesavibul Nattaporn , Phasukkijwatana Nopasak , Prakhunhungsit Supalert , Boonsopon Sutasinee
Published: December 2022

Purpose

This paper aims to propose a solution for detecting and grading diabetic retinopathy (DR) in retinal images using a convolutional neural network (CNN)-based approach. It could classify input retinal images into a normal class or an abnormal class, which would be further split into four stages of abnormalities automatically.

Design/methodology/approach

The proposed solution is developed based on a newly proposed CNN architecture, namely, DeepRoot. It consists of one main branch, which is connected by two side branches. The main branch is responsible for the primary feature extractor of both high-level and low-level features of retinal images. Then, the side branches further extract more complex and detailed features from the features outputted from the main branch. They are designed to capture details of small traces of DR in retinal images, using modified zoom-in/zoom-out and attention layers.

Findings

The proposed method is trained, validated and tested on the Kaggle dataset. The regularization of the trained model is evaluated using unseen data samples, which were self-collected from a real scenario from a hospital. It achieves a promising performance with a sensitivity of 98.18% under the two classes scenario.

Originality/value

The new CNN-based architecture (i.e. DeepRoot) is introduced with the concept of a multi-branch network. It could assist in solving a problem of an unbalanced dataset, especially when there are common characteristics across different classes (i.e. four stages of DR). Different classes could be outputted at different depths of the network.