bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure management through application-based telehealth platforms: a systematic review and meta-analysis
Authors: Kalagara Roshini , Chennareddy Susmita , Scaggiante Jacopo , Matsoukas Stavros , Bhimani Abhiraj , Smith Colton , Putrino David , Dangayach Neha S. , Mocco J. , Schnipper Jeffrey L. , Auerbach Andrew D. , Kellner Christopher P.
Published: June 2022

Background and objectives:

Hypertension management has several challenges, including poor compliance with medications and patients being lost to follow-up. Recently, remote patient monitoring and telehealth technologies have emerged as promising methods of blood pressure management. We aimed to investigate the role of application-based telehealth programs in optimizing blood pressure management.

Methods:

Searches were performed in December 2020 using three databases: Cochrane Central Register of Controlled Trials, Embase and Ovid MEDLINE. All randomized controlled trials that included remote blood pressure management programmes were eligible for inclusion. Studies were included if blood pressure data were available for both the intervention and control groups. Following PRISMA guidelines, data were independently collected by two reviewers. Data were pooled using a random-effects model. The primary study outcomes were mean SBP and DBP changes for the intervention and control groups.

Results:

Eight hundred and seventy-nine distinct articles were identified and 18 satisfied inclusion and exclusion criteria. Overall, a mean weighted decrease of 7.07 points (SBP) and 5.07 points (DBP) was found for the intervention group, compared with 3.11 point (SBP) and 3.13 point (DBP) decreases in the control group. Forest plots were constructed and effect sizes were also calculated. Mean change effect sizes of 1.1 (SBP) and 0.98 (DBP) were found, representing 86 and 85% of the intervention group having greater SBP or DBP changes, respectively, when compared with the control group.

Discussion:

Remote patient monitoring technologies may represent a promising avenue for hypertension management. Future research is needed to evaluate the benefits in different disease-based patient subgroups.
Femtosecond Laser-assisted Cataract Surgery in Patients With Prior Glaucoma Surgery
Authors: Salimi Ali , Qi Susan R. , Harasymowycz Paul
Published: June 2022

Précis:

Femtosecond laser-assisted cataract surgery (FLACS) is a safe procedure in glaucomatous eyes with prior glaucoma surgery, evidenced by stable intraocular pressure (IOP) and medication use, acceptable success rate, disease stability, and low complication rates at 1-year postoperative.

Purpose:

The purpose of this study was to assess the 1-year efficacy and safety of FLACS in glaucomatous eyes with prior glaucoma surgery.

Materials and Methods:

Retrospective case series of all consecutive glaucomatous eyes with previous glaucoma surgery that underwent FLACS using the Catalys Precision Laser System with or without concomitant glaucoma surgery at a single ophthalmology center, between 2014 and 2020. Efficacy included change in IOP, glaucoma medication use, best-corrected visual acuity, and surgical success at 12 months postoperatively (POM12). Safety included structural and functional measures of disease stability and postoperative adverse events.

Results:

A total of 57 eyes with an average age of 62.6±8.1 years were included. At POM12, IOP decreased from 14.5±6.6 mmHg to 13.5±3.7 mm Hg (P=0.22) and glaucoma medication use decreased from 2.1±1.5 to 1.8±1.4 with a marginal significance (P=0.089). Best-corrected visual acuity improved significantly in both groups (P<0.001) and surgical success ranged between 74% and 90% according to the study’s success criteria. Safety was favorable with disease stability evidenced by lack of deterioration in cup-to-disc ratio, visual field mean deviation, retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness. One eye with prior history of trabeculectomy experienced transient bleb leak. Other adverse events were minor without sight-threatening sequelae.

Conclusions:

The results of this study suggest that FLACS with or without concomitant glaucoma surgery could be a safe procedure in glaucomatous eyes—a population for which FLACS has been relatively contraindicated. Nonetheless, in those with preexisting filtering bleb, extra attention should be paid to the bleb area.
Liver Enzyme Elevation Related to Human Parainfluenza Virus Type 3 Infection
Authors: Kudo Yoshimasa , Wakabayashi Tomohiro , Miyamoto Shuichi , Sasaoka Yuta , Sakai Yoshiyuki , Tsugawa Takeshi
Published: June 2022

The human parainfluenza viruses are common causes of upper and lower respiratory tract infection; however, nonrespiratory infections with human parainfluenza viruses are rare, and there are no reports of pediatric cases of liver enzyme elevation. We present 2 pediatric patients who developed liver enzyme elevation related to human parainfluenza virus type 3 infection.
Carbohydrate intake – current knowledge on weight management
Authors: Bayer Sandra , Holzapfel Christina
Published: June 2022

Purpose of review

Carbohydrates are the main contributor to daily energy intake and, thus, might play an essential role in the development and treatment of obesity. This nonsystematic literature overview summarized current knowledge about the association between carbohydrate intake (quantity and quality) and weight management.

Recent findings

There is scientific evidence for the association between the quality of carbohydrates and body weight or metabolic parameters (e.g. fasting glucose). Thus, dietary intake of high-quality carbohydrates should be preferred over food with a low carbohydrate quality. In contrast, heterogeneous data are available for the association between the amount of carbohydrate intake and anthropometric parameters (e.g. body weight, body fat). Regulation of dietary intake and body weight is complex. For instance, gene-diet interactions might play a role in carbohydrate intake and metabolism.

There is evidence for the association between intake of high-quality carbohydrates and body weight. However, for the treatment of obesity, a negative energy balance is crucial. The success in weight loss was independent of the quantity and quality of carbohydrate intake. To sum up, recently published literature does not change the current opinion about carbohydrate intake and obesity.
Adrenal neuroendocrine carcinoma not responsive to EP regimen (cisplatin and etoposide)
Authors: Liu Kai , Zhuang Jiayi
Published: June 2022

Introduction:

Neuroendocrine carcinoma is a malignant tumor that mostly occurs in the digestive tract and lungs but rarely occurs in the adrenal gland. It has a high degree of malignancy and poor prognosis. At present, there is lack of standard treatment protocols.

Patient concerns:

A 41-year-old woman presented with symptoms of repeated cough of one-month duration.

Diagnosis:

Laboratory tests, enhanced computed tomography imaging, and pathology confirmed the diagnosis of adrenal neuroendocrine carcinoma.

Interventions:

A chemotherapy regimen of cisplatin, etoposide (30 mg cisplatin d1–4+ 0.1 g etoposide d1–4) was formulated after multidisciplinary discussion.

Outcomes:

On the second day after the end of chemotherapy, the patient presented with bilateral lower extremity edema, decreased albumin, increased liver enzymes, new thrombus formation in the inferior vena cava and right external iliac vein, right pleural effusion and peritoneal effusion. Three episodes of convulsions of unknown cause occurred 22 days after the end of chemotherapy. L3 vertebral bone metastasis appeared 4 months after admission. Renal function deteriorated and multiple tumor metastases occurred throughout the body. The patient died 4 months and 10 days after admission.

Conclusion:

The prognosis of adrenal neuroendocrine carcinoma is extremely poor, and most patients have distant metastases. Chemotherapy regimens may be ineffective for some patients, and more clinical studies are needed to evaluate the effective treatment options.
Clinical effects of acupuncture on the treatment of delayed sleep wake phase disorder (DSWPD)
Authors: Yu XinTong , Li JinJin , Yang WenJia , Zhao Na , Zhang ChunYan , Chen XinYu , Liu Zhen , Xie Chen , Chen YunFei
Published: June 2022

Background:

Delayed sleep–wake phase disorder (DSWPD) is a circadian rhythm sleep disorder. People with DSWPD fall asleep approximately 2 to 6hours later than those with normal sleep patterns, negatively affecting their ability to learn and work. According to some randomized controlled trials, acupuncture can effectively treat sleep disorders; however, no study has focused specifically on DSWPD. We verified the efficacy of acupuncture in patients with DSWPD by designing an randomized controlled trials with a sufficient sample size, and formed the basis for an improved acupuncture treatment protocol.

Method/Design:

This protocol describes a randomized, single-site, double-blind, sham-controlled trial in which 84 eligible participants will be enrolled and randomly distributed to either the acupuncture group (n = 42) or the sham acupuncture group (n = 42) in a 1:1 proportion. Participants will receive 20 treatment sessions over eight consecutive weeks. Sleep quality was evaluated by using the Pittsburgh Sleep Quality Index. The sleep parameters recorded will be used to measure the secondary results using actigraphy, the Morningness-Eveningness Questionnaire, Insomnia Severity Index Scale, Epworth Sleepiness Scale, Beck Depression Inventory, and Beck Anxiety Inventory. Primary outcomes and actigraphy will be evaluated at baseline, week 4, week 8, and at the first and third month after treatment.

Discussion:

We hypothesize that the outcomes of the proposed study will determine that acupuncture is efficient and secure for the treatment on DSWPD. Evidence for its clinical use could be provided by this positive result.

Trial registration:

Chinese Clinical Trial Registry, ChiCTR2000039450. Registered on October 28, 2020.
Malpractice lawsuits in orthopedic trauma surgery: a meta-analysis of the literature
Authors: Thabet Ahmed M. , Adams Austin , Jeon Soyoung , Pisquiy John , Gelhert Rick , DeCoster Thomas A. , Abdelgawad Amr
Published: June 2022

Introduction:

The objectives for this study were to identify whether diagnostic or procedural errors more commonly resulted in lawsuit, as well as to elucidate how specific variables affected mean indemnity.

Methods:

Systematic review of English-language articles in the PubMed and Google Scholar databases (through 2020) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed to estimate measures of proportions and differences in mean indemnity.

Results:

The estimated probability of lawsuits related to orthopedic trauma in overall studies was 23.3%. There were no significant rate differences between main causes of claims (diagnostic vs procedural errors) and areas of injury (upper vs lower). There was no significant difference of mean indemnity between the probabilities of trauma-related claims, diagnostic error, and procedural error.

Conclusion:

Non-trauma cases were more likely to result in lawsuit than trauma cases. Procedural errors accounted for most malpractice claims. The average indemnity increased according to the higher diagnostic errors, while the indemnity was lower with a relatively higher proportion of procedural errors. The most common cause of litigation varied between studies; however, among the most cited reasons were missed diagnosis/error in diagnosis, improper/substandard surgical performance, and, though not specifically studied in this analysis, errors of informed consent.

Level of Evidence:

Economic and Decision Analyses Level VI
Characteristics and Outcomes of COVID-19 Survivors Requiring Inpatient Rehabilitation: A Comparison of Two Waves
Authors: Gabunia Sergo , Harmon Erin Y. , Sonagere Matthew B. , Teale Amy E.
Published: June 2022

Objective

Many survivors of severe or critical COVID-19 have required rehabilitation during the pandemic. The primary objective was to compare characteristics and outcomes of survivors of severe or critical COVID-19 admitted to the inpatient rehabilitation facility (IRF) during the first two waves of the pandemic. Our secondary objective was to identify the factors contributing to functional dependence on admission, discharge and length of stay.

Design

Retrospective cohort study of 138 patients admitted to an IRF in two waves following hospitalization for severe or critical COVID-19 illness between April 1, 2020 and May 3, 2021.

Results

IRF patients in wave 2 had significantly greater functional independence (GG scores) on admission (52, IQR:44-58 versus 41, IQR: 28-52), lower incidence of dysphagia and anemia. Patients in both waves experienced similar functional improvement efficiencies with a median GG score change of 3.6 per day and similar discharge GG scores. Neurological sequela (OR: 0.12, P < 0.001) and anemia (OR: 1.35, P < 0.002) were identified as independent predictors of functional independence on admission.

Conclusion

Patients with functional deficits after COVID-19 should be considered for acute inpatient rehabilitation as both patient cohorts benefited from their IRF stays with similar length of stays (11-12 days) and discharge to home rates (88- 90%).
An Innovative Simulation Model for Microvascular Training
Authors: Zucal Isabel , Feder Anna-Lena , Kyaw Thura , Khin Sopyay , Heidekrueger Paul I. , Prantl Lukas , Haerteis Silke , Aung Thiha
Published: June 2022

Preclinical/clinical microsurgical training is essential for clinical practice. Therefore, various training models have been established, such as synthetic and cadaveric models. The most common limitation of these models is the lack of circulation, which limits the simulation of real intraoperative circumstances. Thus, the authors aimed to create a novel model that provides blood circulation with an extracorporeal perfusion device that they attached to rat cadavers for the reestablishment of a circulatory system. Patent blue and heparin were added to the perfusion fluid to visualize circulation and to dissolve thrombosis, and indocyanine green fluorescent imaging was applied to show the perfusion of the entire body. The femoral and brachial vessels were dissected, and an end-to-end anastomosis was performed on the femoral artery. The patency of the operated vessel was visualized with indocyanine green fluorescent imaging. Indocyanine green fluorescent imaging showed appropriate vessel patency and extremity perfusion through the anastomosis. The use of this novel rat model enables a solution for ethical problems encountered when using rats for surgical training courses. By practicing on these animal-sparing models with intact circulation, microsurgical skills can be improved. Future studies on further microsurgical techniques and vascular perfusion of organs or tumors may benefit from our model.
Tongue Flap for Management of Large Palatal Fistulas
Authors: Giugliano Carlos , Roldán Nicole , Claure Pilar , Suarez Vivian
Published: June 2022

One of the worst complications after a primary palatoplasty is the lesion of the neurovascular bundle, results into a type of flap necrosis, having as a final consequence a residual palatine fistula.

In our institution the authors usually use tongue flap to repair large fistulas.

The authors retrospectively reviewed all patients with large palatal fistulas that were repaired with tongue flap at Fundacion Gantz between January 2002 and December 2020.

Fundacion Gantz has 1.067 patients with palatal surgeries, with an incidence of 5,8% for palatal fistulas and 3,2% (n = 2) were considered large.

Surgery was done on 24 patients with large residual palatal fistula, all of them with tongue flaps as outpatient surgery. Fifteen were girls and 9 were boys, between 13 and 40 years.

The average size of the fistula was 2,5 cm and 100% are localized in the anterior palate.

The incidence of complications with tongue flap was 12, 5%: 2 dehiscences and 1 persistent residual fistula. The authors had no complications in phonation due to the lingual donor area.

The authors consider that this outpatient surgery, is a reprodutible and safe technique, with a low rate of complications, which allows us to recommend it for the treatment of large palatal fistulas.
The Use of the Three-Dimensional Printed Polyether Ether Ketone Implant in Secondary Craniosynostosis Revision
Authors: Atamian Elisa K. , Hazkour Nissim , Palacios Jose , Pessino Kenneth , Raza Syed A. , Schneider Steven J. , Bastidas Nicholas
Published: June 2022

Background:

Skull deformities may be seen in patients years after craniosynostosis correction. These deformities cause psychosocial distress in affected patients. In this series, the authors describe the use of patient specific polyether ether ketone (PEEK) implants for correction of skull deformities after cranial vault remodeling for craniosynostosis.

Methods:

A chart review was conducted for 3 revision procedures performed by 1 plastic surgeon in collaboration with 1 neurosurgeon, both affiliated with Northwell Health. Preoperative computed tomography scans were used to design three-dimensional (3D) printed PEEK implants manufactured by KLS Martin. Implants were used to correct frontal and orbital asymmetry and skull deformities in each patient. Outcomes were assessed at 1 week, 1 month, and 3 months post-operation.

Results:

Two males and 1 female, ages 13, 17, and 19, underwent revision cranioplasty or orbital rim reconstruction using a custom, single piece 3D printed PEEK implant. All 3 patients underwent cranial vault remodeling in infancy; 1 was treated for coronal craniosynostosis and 2 were treated for metopic craniosynostosis. Revision cranioplasty operative times were 90, 105, and 147 minutes, with estimated blood loss of 45 mL, 75 mL, and 150 mL, respectively. One patient went home on post op day 1 and 2 patients went home on post op day 2. All patients had an immediate improvement in structural integrity and cranial contour, and all patients were pleased with their aesthetic results.

Conclusions:

Custom 3D printed PEEK implants offer a single piece solution in revision cranioplasty surgery to correct skull deformities after cranial vault remodeling for craniosynostosis.
Continuous Interstitial Glucose Measurement for Flap Venous Occlusion Monitoring in a Diabetic Model
Authors: Zhang Chang , Wang Qianwen , Wu Lehao , Wang Jue , Zhao Sichun , Wang Jiaqi
Published: June 2022

Glucose has been used in the monitoring of transplanted flaps. However, few studies have focused on the effect of diabetes on the decrease in flap glucose levels. The purpose of this study was to evaluate the application of continuous interstitial glucose monitoring to detect flap venous occlusion in a diabetic rat model. The flap interstitial glucose level was measured by transcutaneous sensors in the bilateral vertical rectus abdominis myocutaneous flaps of each rat. interstitial glucose values in the bilateral flaps were recorded every 5 minutes after the venous occlusion of 1 flap. Forty-one rats were divided into the control group (n = 13), diabetic group (n = 15, established by the intraperitoneal injection of streptozotocin), and insulin-treated diabetic group (n = 13, systemic glucose well controlled by insulin before surgery). Results indicated that flap interstitial glucose decreased to the lowest level in all flaps with venous occlusion. The time from venous occlusionto the lowest interstitial glucose level was significantlylongerinthe diabetic group than the control group (120.8 ± 5.7 minutes versus 56.5 ± 6.7 min-minutes, P < 0.001), but was similar in the insulin-treated diabetic and control groups (56.5 ± 6.7 minutes versus 56.0 ± 6.6 minutes, P = 0.876). The change in interstitial glucose in both the diabetic and insulin-treated diabetic groups began with a plateau period or a slow decline before decreasing for 49.0 ± 6.4 minutes and 24.4 ± 4.3 min-minutes, respectively. in a diabetic rat model, impaired glucose metabolism prolongs the required monitoring time and dulls the reaction of flap interstitial glucose to venous congestion. Insulin restores the prolonged monitoring time, but not the reaction of flap interstitial glucose. Therefore, care is needed during application of the technique in diabetic patients.
Cadaveric Bone Allografting for Severe Mandibular Hypoplasia With Alleviation of Upper Airway Obstruction in Goldenhar Syndrome
Authors: Villavisanis Dillan F. , Blum Jessica D. , Cho Daniel Y. , Taylor Jesse A.
Published: June 2022

Severe congenital mandibular hypoplasia may cause significant upper airway obstruction, often necessitating immediate tracheostomy. Recent surgical advances have demonstrated early intervention with mandibular distraction osteogenesis over tracheostomy may yield desirable aesthetic and functional outcomes. Here we present a case of bilateral mandibular hypoplasia, severe on the right and mild on the left, secondary to Goldenhar syndrome yielding significant tongue-based upper airway obstruction that was surgically corrected with mandibular bone allograft reconstruction of the right condyle, ramus, and posterior half of the mandibular body. Postoperative polysomnography revealed significantly improved obstructive apnea and computed tomography demonstrated adequate placement of the bone allograft to overcorrect the affected hemi-mandible. To the authors’ knowledge, this is the first report of immediate mandibular allografting alleviating tongue-based upper airway obstruction secondary to mandibular hypoplasia in an infant. Mandibular bone allografting may be a favorable alternative to immediate tracheostomy with delayed surgical intervention, though long-term follow up is needed to assess graft durability and maintenance of airway patency.
The Kidney Transplant Equity Index
Authors: Delman Aaron M. , Turner Kevin M. , Silski Latifa S. , Quillin Ralph C. , Estrada Martha , Lemon Kristina , Cuffy Madison C. , Shah Shimul A.
Published: June 2022

Objectives:

To develop a scalable metric which quantifies kidney transplant (KT) centers’ performance providing equitable access to KT for minority patients, based on the individualized prelisting prevalence of end-stage renal disease (ESRD).

Background:

Racial and ethnic disparities for access to transplant in patients with ESRD are well described; however, variation in care among KT centers remains unknown. Furthermore, no mechanism exists that quantifies how well a KT center provides equitable access to KT for minority patients with ESRD.

Methods:

From 2013 to 2018, custom datasets from the United States Renal Data System and United Network for Organ Sharing were merged to calculate the Kidney Transplant Equity Index (KTEI), defined as the number of minority patients transplanted at a center relative to the prevalence of minority patients with ESRD in each center’s health service area. Markers of socioeconomic status and recipient outcomes were compared between high and low KTEI centers.

Results:

A total of 249 transplant centers performed 111,959 KTs relative to 475,914 nontransplanted patients with ESRD. High KTEI centers performed more KTs for Black (105.5 vs 24, P<0.001), Hispanic (55.5 vs 7, P<0.001), and American Indian (1.0 vs 0.0, P<0.001) patients than low KTEI centers. In addition, high KTEI centers transplanted more patients with higher unemployment (52 vs 44, P<0.001), worse social deprivation (53 vs 46, P<0.001), and lower educational attainment (52 vs 43, P<0.001). While providing increased access to transplant for minority and low socioeconomic status populations, high KTEI centers had improved patient survival (hazard ratio: 0.86, 95% confidence interval: 0.77–0.95).

Conclusions:

The KTEI is the first metric to quantify minority access to KT incorporating the prelisting ESRD prevalence individualized to transplant centers. KTEIs uncover significant national variation in transplant practices and identify highly equitable centers. This novel metric should be used to disseminate best practices for minority and low socioeconomic patients with ESRD.
Factors Associated With COVID-19 Vaccine Response in Transplant Recipients: A Systematic Review and Meta-analysis
Authors: Li Jiajing , Ayada Ibrahim , Wang Yining , den Hoed Caroline M. , Kamar Nassim , Peppelenbosch Maikel P. , de Vries Annemarie C. , Li Pengfei , Pan Qiuwei
Published: June 2022

Background.

The rapid development and universal access to vaccines represent a milestone in combating the coronavirus disease 2019 (COVID-19) pandemic. However, there are major concerns about vaccine response in immunocompromised populations in particular transplant recipients. In the present study, we aim to comprehensively assess the humoral response to COVID-19 vaccination in both orthotopic organ transplant and allogeneic hematopoietic stem cell transplant recipients.

Methods.

We performed a systematic review and meta-analysis of 96 studies that met inclusion criteria.

Results.

The pooled rates of seroconversion were 49% (95% confidence interval [CI], 43%-55%) in transplant recipients and 99% (95% CI, 99%-99%) in healthy controls after the second dose of vaccine. The pooled rate was 56% (95% CI, 49%-63%) in transplant recipients after the third dose. Immunosuppressive medication is the most prominent risk factor associated with seroconversion failure, but different immunosuppressive regimens are associated with differential outcomes in this respect. Calcineurin inhibitors, steroids, or mycophenolate mofetil/mycophenolic acid are associated with an increased risk of seroconversion failure, whereas azathioprine or mammalian target of rapamycin inhibitors do not. Advanced age, short interval from receiving the vaccine to the time of transplantation, or comorbidities confers a higher risk for seroconversion failure.

Conclusions.

Transplant recipients compared with the general population have much lower rates of seroconversion upon receiving COVID-19 vaccines. Immunosuppressants are the most prominent factors associated with seroconversion, although different types may have differential effects.
MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
Authors: Lu Ping , Zhao Yonghui , Xie Zili , Dong Xinzhong , Wu Gregory F. , Kim Brian S. , Feng Jing , Hu Hongzhen
Published: June 2022

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3- expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function through activation of the PLC-PKCδ signaling. Collectively, our data uncovered a TRPV1+/MrgprA3+prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensitization in the skin.
The guanine nucleotide exchange factor Rin-like acts as a gatekeeper for T follicular helper cell differentiation via regulating CD28 signaling
Authors: Sandner Lisa , Alteneder Marlis , Rica Ramona , Woller Barbara , Sala Eleonora , Frey Tobias , Tosevska Anela , Zhu Ci , Madern Moritz , Hoffmann Pol , Schebesta Alexandra , Taniuchi Ichiro , Bonelli Michael , Schmetterer Klaus , Iannacone Matteo , Kuka Mirela , Ellmeier Wilfried , Sakaguchi Shinya , Herbst Ruth , Boucheron Nicole
Published: June 2022

T follicular helper (Tfh) cells are essential for the development of germinal center B cells and high-affinity antibody producing B-cells in human and mice. Here, we identify the guanine nucleotide exchange factor (GEF) Rin-like (Rinl) as a negative regulator of Tfh generation. Loss of Rinl leads to an increase of Tfh in aging, uponin vivoimmunization and acute LCMV Armstrong infection in mice, and in human CD4+T cellin vitrocultures. Further, adoptive transfer experiments using WT and Rinl-KO naïve CD4+T cells unraveled T cell-intrinsic functions of Rinl. Mechanistically, Rinl regulates CD28 internalization and signaling, thereby shaping CD4+T cell activation and differentiation. Thus, our results identify the GEF Rinl as a negative regulator of global Tfh differentiation in an immunological context and species-independent manner, and furthermore connect Rinl with CD28 internalization and signaling pathways in CD4+T cells, demonstrating for the first-time the importance of endocytic processes for Tfh differentiation.

Highlights

Rinl-KO CD4+T cells show increased Tfh differentiation in a context independent manner

The regulation of Tfh differentiation is T cell-intrinsic

Rinl controls CD28 endocytosis and shapes Tfh-specific CD28 signal transduction

Human Tfh differentiation is regulated by Rinl
An evaluation of the introduction of telehealth for remote antenatal and postnatal contacts in Bangladesh and Lao People’s Democratic Republic during the COVID-19 pandemic
Authors: Turkmani Sabera , Smith Rachel M , Tan Annie , Kamkong Catherine Breen , Anderson Rondi , Sakulku Siriphone , Jat Tej Ram , Biswas Animesh , Homer Caroline SE
Published: June 2022

From 2020, COVID-19 spread rapidly around the globe and continues to have a major impact on health system functioning, with a disproportionate impact on low- and middle-income countries (LMIC). Reduced service utilisation and coverage of essential childbirth interventions is likely impacting maternal and newborn morbidity and mortality. Telehealth has been identified as an important tool in the continued provision of essential health care services. The aim of this study was to explore the experience and impact of implementing telehealth services for the provision of remote antenatal (ANC) and postnatal (PNC) contacts in regions of Bangladesh and Lao People’s Democratic Republic through 100 semi-structured interviews with health service leaders and providers, and childbearing women who organised, provided, or were the recipients of ANC and PNC telehealth during the COVID-19 pandemic response. The findings showed that a sudden pivot from face-to-face to telehealth services posed health system and care was challenging. Health systems lacked funding to support telehealth and the infrastructure needed for service changes; however, some were able to work with key maternal child health departments within Ministries of Health to find the resources to implement the services. Health providers found telehealth beneficial during the pandemic response but identified a lack of training, guidance, and support as a barrier to changing practice. Childbearing women reported being fearful of accessing care at health services due to COVID-19, and whilst they appreciated the telehealth contacts, many continued to prefer face-to-face delivery of ANC and PNC care. Telehealth, however, was a good alternative in a time when face-to-face care was not possible. Considerations for post-pandemic broader implementation or scale-up of telehealth for routine ante natal and post natal maternity care provision include the need for further research on issues such as accessibility, acceptability, quality of care, and sustainability of service provision.
Biosphere functional integrity for people and Planet
Authors: Mohamed Awaz , DeClerck Fabrice , Verburg Peter H. , Obura David , Abrams Jesse F. , Zafra-Calvo Noelia , Rocha Juan , Estrada-Carmona Natalia , Fremier Alexander , Jones Sarah K. , Meier Ina C. , Stewart-Koster Ben
Published: June 2022

Defining a safe and just biosphere space requires a synthetic scaleable measure of biosphere functional integrity to secure Nature’s Contributions to People (NCP). Using a systematic review of 153 peer-reviewed studies we estimated the minimum level of functional integrity needed to secure multiple critical NCP, including pollination, pest and disease control, water quality regulation, soil protection, recreation and natural hazards mitigation in human-modified landscapes. We characterise functional integrity by the quantity, quality and spatial configuration of (semi-)natural habitat within any landscape. We find that at least 20-25% of structurally complex and biologically diverse (semi-)natural habitat in each 1 km2of land area is needed to maintain the supply of multiple NCP simultaneously. Exact quantity, quality and spatial configuration required is dependent on local context, and may differ for individual NCP. Today, about 50-60% of human-modified lands have less than 10% and 20% (semi-)natural habitat per 1 km2respectively. These areas require immediate attention to regenerate functional integrity in order to secure ecological functioning in those landscapes.
Transition to self-compatibility associated with dominantS-allele in a diploid Siberian progenitor of allotetraploidArabidopsis kamchaticarevealed byArabidopsis lyratagenomes
Authors: Kolesnikova Uliana K. , Scott Alison Dawn , Van de Velde Jozefien D. , Burns Robin , Tikhomirov Nikita P. , Pfordt Ursula , Clarke Andrew C. , Yant Levi , Seregin Alexey P. , Vekemans Xavier , Laurent Stefan , Novikova Polina Yu.
Published: June 2022

A transition to selfing can be beneficial when mating partners are scarce, for example, due to ploidy changes or at species range edges. Here we explain how self-compatibility evolved in diploid SiberianArabidopsis lyrata,and how it contributed to the establishment of allotetraploidA. kamchatica. First, we provide chromosome-level genome assemblies for two self-fertilizing diploidA. lyrataaccessions, one from North America and one from Siberia, including a fully assembled S-locus for the latter. We then propose a sequence of events leading to the loss of self-incompatibility in SiberianA. lyrata,date this independent transition to ∼90 Kya, and infer evolutionary relationships between Siberian and North AmericanA. lyrata,showing an independent transition to selfing in Siberia. Finally, we provide evidence that this selfing SiberianA. lyratalineage contributed to the formation of the allotetraploidA. kamchaticaand propose that the selfing of the latter is mediated by the loss-of-function mutation in a dominantS-allele inherited fromA. lyrata.
Consensus genomic regions associated with multiple abiotic stress tolerance in wheat and implications for wheat breeding
Authors: Tanin Mohammad Jafar , Saini Dinesh Kumar , Sandhu Karansher Singh , Pal Neeraj , Gudi Santosh , Chaudhary Jyoti , Sharma Achla
Published: June 2022

In wheat, a meta-analysis was performed using previously identified QTLs associated with drought stress, heat stress, salinity stress, water-logging stress, pre-harvest sprouting, and aluminium stress which predicted a total of 134 meta-QTLs (MQTLs) that involved at least 28 consistent and stable MQTLs conferring tolerance to five or all six abiotic stresses under study. Seventy-six MQTLs out of the 132 physically anchored MQTLs were also verified with genome-wide association studies. Around 43% of MQTLs had genetic and physical confidence intervals of less than 1 cM and 5 Mb, respectively. Consequently, 539 genes were identified in some selected MQTLs providing tolerance to 5 or all 6 abiotic stresses. Comparative analysis of genes underlying MQTLs with four RNA-seq based transcriptomic datasets unravelled a total of 191 differentially expressed genes which also included at least 11 most promising candidate genes common among different datasets. The promoter analysis showed that the promoters of these genes include many stress responsiveness cis-regulatory elements, such as ARE, MBS, TC-rich repeats, As-1 element, STRE, LTR, WRE3, and WUN-motif among others. Further, some MQTLs also overlapped with as many as 34 known abiotic stress tolerance genes. In addition, numerous ortho-MQTLs among the wheat, maize, and rice genomes were discovered. These findings could help with fine mapping and gene cloning, as well as marker-assisted breeding for multiple abiotic stress tolerances in wheat.
The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell-infected cell contacts
Authors: Peauroi Elise M. , Carro Stephen D. , Pei Luxin , Reynoso Glennys V. , Hickman Heather D. , Eisenlohr Laurence C.
Published: June 2022

The success of poxviruses as pathogens depends upon their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation. Here, we demonstrate by quantitative immunofluorescence imaging that C15 also limits contact between natural killer (NK) cells and infected cells in vivo. This corresponds to an inhibition in the number of total and degranulating NK cells, ex vivo and in vitro, with no detectable impact on NK cell cytokine production nor the transcription of factors related to NK cell recruitment or activation. Thus, in addition to its previously identified capacity to antagonize CD4 T cell activation, C15 inhibits NK cell cytolytic function, which results in increased viral replication and dissemination in vivo. This work builds on a body of literature demonstrating the importance of early restriction of virus within the draining lymph node.

summary

Poxvirus B22 family proteins are important virulence factors known to inhibit T cell functions. Peauroi et al. identify a novel function of the ectromelia virus homolog, C15, which inhibits NK cell-target contact and cytolytic function to facilitate early viral spread.

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Efficacy of Jiedu Tongluo Tiaogan Formula on Type 2 Diabetic Lower Extremity Arteriosclerosis Obliterans: Study Protocol for a Metabolomics-Based Randomized Controlled Clinical Trial
Authors: Liu Tianjiao , Piao Chunli , Peng Yuting , Xu Jinghan , Qu Yue , Li Qi , Zhao Xiaohua , Wu Xuemin , Li Pei , Fan Yawen
Published: June 2022

Introduction

Diabetic lower extremity arteriosclerosis obstruction (DLASO) is a common macrovascular complication in type 2 diabetic mellitus (T2DM), which can cause amputations and a higher risk of cardiovascular events. However, there are few effective treatments for DLASO currently. To evaluate the safety and efficacy of Jiedu Tongluo Tiaogan Formula (JTTF) in type 2 diabetic lower extremity arteriosclerosis obliterans and looking for a mechanism of action, we designed a clinical trial and mechanism exploration based on metabolomics technology.

Methods and Analysis

This study is designed as a randomized controlled clinical trial. A total of 80 participants will be recruited and randomized to a TCM group (JTTF + essential treatments) and a control group (essential treatments) in a ratio of 1:1. The treatment duration is 12 weeks. Changes in clinical symptom scores, color ultrasound Doppler hemodynamics of lower extremity arteries, and Ankle-Brachial Ratio (ABI) will be the primary outcomes. Changes in TCM symptoms scores, other indicators related to arteriosclerosis, blood glucose, lipids, and body mass will be the secondary outcomes. The primary and secondary outcomes will be evaluated at baseline and week 12. Safety outcomes and adverse events will also be properly assessed. After treatment completion, blood and urine samples from subjects will be tested for metabolomics.

Discussion

This study aims to verify the efficacy and safety of JTTF in type 2 diabetic lower extremity arteriosclerosis obliterans and obtain the key action pathway. It helps to provide scientific evidence for TCM treatment of diabetic vascular complications.

Ethics and Dissemination

This trial has been approved by the Ethics Committee (GZYLL(KY)-2021-024). Results of this trial will be published in journals and presented at scientific conferences. We share raw data in the ResMan network platform. All the authors declare that they have no conflicts of interest.

Trial registration

Chinese Clinical Trials Register, ChiCTR2100051337. Registered on 20 September 2021.
Recent-Onset and Persistent Tinnitus: Uncover the Differences in Brain Activities using Resting-State Functional Magnetic Resonance Imaging Technologies
Authors: Du Haoliang , Feng Xu , Qian Xiaoyun , Zhang Jian , Liu Bin , Li Ao , Huang Zhichun , Gao Xia
Published: June 2022

Objective

This project aimed to investigate the differences in the intra-regional brain activity and inter-regional functional connectivity between patients with recent-onset tinnitus and persistent tinnitus using resting-state functional magnetic resonance imaging (rs-fMRI) technologies, including the Amplitude of Low-Frequency Fluctuations (ALFF), regional homogeneity (ReHo), and Voxel-Wise Functional Connectivity (FC).

Method

We acquired rs-fMRI scans from 82 subjects (25 subjects without recent-onset tinnitus, 28 subjects with persistent tinnitus, and 29 subjects as healthy control). Age, gender, and year of education were matched across all three groups. We performed ALFF, ReHo, and Voxel-Wise Functional Connectivity (FC) for all subjects.

Result

Compared with the control group (CN), subjects with recent-onset tinnitus (ROT) and with persistent tinnitus (PT) manifested significantly reduced ALFF and ReHo activity within the left and right dorsolateral superior frontal gyrus (SFG) and Gyrus Rectus (GR). Additional Voxel-Wise Functional Connectivity (FC) revealed decreased connectivity between the dorsolateral SFG (left and right) and right Superior Parietal Gyrus (SPG), right Middle Frontal Gyrus (MFG), and left medial Superior Frontal Gyrus (mSFG) within these two groups. Significant differences were observed between the ROT and PT groups, with the ROT group demonstrating reduced functional connectivities.

Conclusion

Upon analyzing our data, we suggested that patients with persistent tinnitus have more difficulty monitoring external stimuli and reorienting attention than patients with recent-onset tinnitus. In addition, patients who perceive higher levels of disruption from tinnitus are more likely to develop persistent and debilitating tinnitus once the tinnitus lasts longer than six months. Therefore, we strongly recommend that clinicians implement effective tinnitus management strategies for patients with recent-onset tinnitus as soon as possible.
Convergent Gene Expression Patterns During Compatible Interactions Between TwoPseudomonas syringaePathovars and a Common Host (Nicotiana benthamiana)
Authors: Carter Morgan E. , Smith Amy , Baltrus David A. , Kvitko Brian H.
Published: June 2022

Summary/Abstract

Pseudomonas syringaeis a diverse phytopathogenic species complex, and includes strains that can cause disease across a wide variety of plant species. Much previous research into the molecular basis of immunity and infection has focused on pathogen and plant responses in a handful of model strains and hosts, and with a tacit assumption that early steps in infection and host resistance are generalizable to the species complex and across plant hosts as a whole. Here, we provide a test of this assumption by measuring the dual pathogen and host transcriptomes of two distinct pathogenic lineages ofP. syringaeduring compatible infection of a shared model host (Nicotiana benthamiana). Our results demonstrate that, with a handful of exceptions, host plants largely respond in a similar way to both pathogenic lineages and both bacterial pathogens possess highly similar transcriptional responses at 5 hours post inoculation. However, we also highlight that subsets of genes with differential expression patterns in both bacteria and host which likely represent strain-specific responses.
Female-specific factors are associated with cognition in the UK Biobank cohort
Authors: Lindseth Linn R.S. , de Lange Ann-Marie G. , van der Meer Dennis , Agartz Ingrid , Westlye Lars T. , Tamnes Christian K. , Barth Claudia
Published: June 2022

Background

Relative to males, females are at a higher risk of developing age-related neurocognitive disorders including Alzheimer’s disease. Emerging evidence suggests that reproductive life events such as pregnancy and hormone use may influence female’s cognition later in life. Yet, female’s health has historically been understudied, and little is known about the relationship between female-specific factors and cognition.

Methods

Using multiple linear regression, we investigated the associations between reproductive history, exogenous hormone use, apolipoprotein (APOE) ε4 genotype and cognition in 221,124 middle-to older-aged (mean age 56.2 ± 8.0 years) females from the UK Biobank. Performance on six cognitive tasks was assessed, covering four cognitive domains: episodic visual memory, numeric working memory, processing speed, and executive function.

Results

A longer reproductive span, older age at menopause, older age at first and last birth, and use of hormonal contraceptives were positively associated with cognitive performance later in life. Number of live births, hysterectomy without oophorectomy and use of hormone therapy showed mixed findings, with task-specific positive and negative associations. Effect sizes were generally small (Cohen’s d < 0.1). While APOE ε4 genotype was associated with reduced processing speed and executive functioning, in a dose-dependent manner, it did not influence the observed associations between female-specific factors and cognition.

Conclusion

Our findings support previous evidence of associations between a broad range of female-specific factors and cognition. The positive association between a history of hormonal contraceptive use and cognition later in life showed the largest effect sizes (max. d = 0.1). Future research is needed to investigate the effects of sex hormone exposure and cognition to develop a better understanding of female’s brain health.