bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, prevention, risk factors, and prediction of venous thromboembolism in chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study
Authors: Wei Qi , Wei Zheng-Qiang , Jing Chang-Qing , Li Yong-Xiang , Zhou Dong-Bing , Lin Mou-Bin , He Xian-Li , Li Fan , Liu Qian , Zheng Jian-Yong , Wang Gui-Ying , Tu Shi-Liang , Wang Zhen-Jun , Li Ang , Xiao Gang , Zhuang Jing , Bai Lian , Huang He , Li Yong , Song Wu , Liang Zhong-Lin , Shen Zhan-Long , Liu Fan-Long , Dai Yong , Zhou Xiao-Jun , Dong Ming , Wang Hui , Qiu Jian , Zhou Lei , Li Xin-Xiang , Wang Zi-Qiang , Zhang Hong , Wang Quan , Pang Ming-Hui , Wei Hong-Bo , Hu Zhi-Qian , Yan Yi-Dan , Che Yan , Gu Zhi-Chun , Yao Hong-Wei , Zhang Zhong-Tao ,   and for the CRC-VTE investigators
Published: June 2023

Background:

Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning.

Methods:

Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for one month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed.

Results:

A total of 1,836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1,210 (65.9%) received pharmacological prophylaxis, and 1,061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95%CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95%CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95%CI 0-0.5). Multifactorial analysis showed that age (≥70 y), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time ≥180 minutes were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance (C-statistic 0.72, 95%CI 0.68-0.76).

Conclusions:

This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.
A Clinical Trial of Treating Androgenic Alopecia with Mesenchymal Stem Cell Suspension Derived from Autologous Hair Follicle
Authors: Gan Yuyang , Du Lijuan , Wang Hailin , Li Kaitao , Fan Zhexiang , Sun Pingping , Zhang Jiaxian , Hu Zhiqi , Miao Yong
Published: June 2023

Background:

Androgenic alopecia (AGA) is characterized by progressive hair follicle miniaturization. Novel treatments are needed to intervene in the miniaturization process. The authors aimed to evaluate the efficacy, safety, effectiveness, and effective population of autologous hair follicle mesenchymal stem cell therapy for the treatment of advanced AGA in Chinese individuals.

Methods:

Fifty patients ranging in age from 25 to 45 years (average, 32 ± 1.24 years) were included. None of them had ever used minoxidil, finasteride, or other drugs to promote hair growth. Healthy hair follicles were extracted from the occipital area and treated to obtain hair follicle mesenchymal stem cell suspensions. The recipient sites were divided into 2 groups. Nine points were injected in a 1-cm2 area, and 100 µL of solution containing either 1 × 105 cells or normal saline was injected at each point. The follow-up duration was 9 months. Observers were blinded to patient groupings and measurements.

Results:

An increased proportion of terminal hair and hair shaft diameter was observed in the experimental group at 1 month. The effect lasted for 3 months. The hair-thickening effect of advanced miniaturized hair follicles with hair shaft diameter less than 60 µm was more notable than that for above 60 µm. No patient experienced any obvious side effects.

Conclusions:

Hair follicle mesenchymal stem cells were effective in the treatment of advanced AGA in Chinese individuals. A hair shaft diameter of 60 µm can be used as a key index to predict the effectiveness of the therapy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Comparative Study of Pharyngeal Flap Outcomes between Children with 22q11.2 Deletion Syndrome and Nonsyndromic Cleft Lip and Palate
Authors: Wang Alice T. , Hseu Anne F. , Staffa Steven J. , Clark Roseanne E. , Meara John G. , Nuss Roger C. , Ganske Ingrid M. , Rogers-Vizena Carolyn R.
Published: June 2023

Background:

Management of velopharyngeal insufficiency (VPI) in 22q11.2 deletion syndrome is challenging. The authors compared pharyngeal flap outcomes in children with 22q11.2 deletion syndrome to those with nonsyndromic cleft lip and palate (CLP) to assess risk of poor speech outcomes and negative sequelae.

Methods:

Children with 22q11.2 deletion syndrome or CLP treated with pharyngeal flap through a multidisciplinary VPI clinic between 2009 and 2020 were retrospectively reviewed. Preoperative and postoperative speech assessments, perioperative characteristics, and complications were identified.

Results:

Thirty-six children with 22q11.2 deletion syndrome and 40 with CLP were included. Age at surgery (P = 0.121), preoperative velopharyngeal competence score (P = 0.702), and preoperative resonance (P = 0.999) were similar between groups. Pharyngeal flaps were wider (P = 0.038) and length of stay longer in the 22q11.2 deletion syndrome group (P = 0.031). On short-term follow-up 4 months after surgery, similar speech outcomes were seen between groups. At long-term follow-up greater than 12 months after surgery, 86.7% of 22q11.2 deletion syndrome versus 100% of CLP (P = 0.122) children had improvement in velopharyngeal function; however, fewer children with 22q11.2 deletion syndrome (60.0%) achieved a completely “competent” velopharyngeal competence score compared with those with CLP (92.6%) (P = 0.016). Nasal regurgitation improved for both groups, with a greater improvement in those with 22q11.2 deletion syndrome (P = 0.026). Revision rate (P = 0.609) and new-onset obstructive sleep apnea (P = 0.999) were similar between groups.

Conclusions:

Children with 22q11.2 deletion syndrome have improved speech after pharyngeal flap, but they may be less likely to reach normal velopharyngeal function over the long term than those with CLP; however, negative sequelae do not differ. Improvement in nasal regurgitation is a uniquely positive outcome in this population.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Outcome Comparisons of Two Different Orbicularis Oris Muscle Reconstruction Techniques in Patients with Unilateral Incomplete Cleft Lip
Authors: Zhang Chong , Yao Meilin , Low David W. , Wu Min , Shi Bing , Zheng Qian , Li Chenghao
Published: June 2023

Background:

The long-term postoperative outcomes of two different orbicularis oris muscle reconstruction techniques in patients with unilateral incomplete cleft lip were compared.

Methods:

Forty-seven patients with unilateral incomplete cleft lip were assessed in this study, where 23 underwent a traditional method of reconstruction and 24 underwent a novel method. Preoperative measurements, postoperative results, and 3-year follow-up outcomes were measured by photographic anthropometric analysis. Five upper lip measurement indices and 8 nostril indices were included.

Results:

The postoperative outcomes showed that the shape of the lip and nose was more symmetric with the new surgical method compared with the conventional technique. Long-term outcomes after 3 years, although characterized by minimal changes during maxillofacial development, showed better maintenance of lip and nostril symmetry in the novel-method group.

Conclusion:

The novel technique seeks to balance the perinasal and perioral muscles, resulting in improved symmetry compared with the traditional reconstruction technique.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A Simplified Approach for Surgical Correction of Vertical Orbital Dystopia: A 45-Year Retrospective Cohort Study
Authors: Wolfe Erin M. , Ainuz Bar Y. , Ragheb John , Wolfe S. Anthony
Published: June 2023

Background:

Vertical orbital dystopia (VOD) results in significant facial asymmetry, psychological distress, and poor quality of life in affected patients. The traditional approach (TA) for surgical correction has entailed a standard frontal craniotomy along with circumferential orbital osteotomy, vertical translocation of the orbit, and bone grafting to the lower maxilla. Caution has been expressed regarding its invasive transcranial nature. In this report, the authors describe the limited approach (LA) for simplified surgical correction of VOD, which obviates the need for a standard frontal craniotomy.

Methods:

A 45-year retrospective review was conducted of all patients who underwent surgical correction of VOD, as performed by a single surgeon. Demographic details, procedural characteristics, and complications were compared between patients who underwent correction by the TA and those who underwent correction by the LA. Complications were defined as cerebrospinal fluid leak, infection of the frontal bone, permanent diplopia, permanent ptosis, sudden-onset vision loss, persistent asymmetry, and surgical revision.

Results:

Forty patients met inclusion criteria for correction of true VOD, of which 18 underwent the TA and 22 underwent the LA. Mean length of hospital stay was 5.3 ± 2.3 days and 4.0 ± 1.5 days for the TA and LA cohorts, respectively. Mean follow-up time was 4.9 ± 7.5 years for the TA cohort and 2.6 ± 3.3 years for the LA cohort. The only reported complications were persistent asymmetry in 2 patients in the TA cohort, with 1 patient requiring surgical revision because of undercorrection, whereas the LA cohort exhibited no postoperative asymmetry or need for surgical revision.

Conclusions:

Both the TA and the LA are effective for surgical correction of VOD. The limited craniotomy of the LA reduces exposure of intracranial structures and adequately achieves postoperative symmetry.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Integration of the CLEFT-Q Patient-Reported Outcome Tool into a Multidisciplinary Cleft and Craniofacial Clinic: A Proof of Concept
Authors: Salinero Lauren K. , Villavisanis Dillan F. , Cheung Liana , Ferro Daria F. , Folsom Nancy , Cho Daniel Y. , Low David W. , Jackson Oksana , Bartlett Scott P. , Swanson Jordan W.
Published: June 2023

Implementation of patient-reported outcome (PRO) tools has increased internationally in a variety of clinical settings, with emerging evidence suggesting benefits for patient satisfaction, improved patient-provider communication, and management of chronic conditions. However, integrating PROs into clinical workflow remains a barrier to implementation, with common challenges including patient completion, provider review of results, and future accessibility of data. Cleft lip and/or palate presents with a variety of aesthetic, functional, and psychosocial sequelae optimally managed by a multidisciplinary team, and the CLEFT-Q is a validated 12-module PRO that captures patient perception in these domains. Given the emerging proven benefits of using PROs in a clinical setting, the authors integrated the CLEFT-Q PRO at a multidisciplinary cleft and craniofacial clinic at a large, urban, tertiary care center. The authors collaborated with their institution’s electronic health record clinical informatics team to automatically identify eligible cleft lip and/or palate patients and generate the CLEFT-Q PRO before weekly multidisciplinary cleft and craniofacial clinic days. Patient results were automatically scored, compared with age-based normative data, and populated into the electronic health record patient note. CLEFT-Q results were viewed by clinicians during patient visits to initiate module-specific discussion in relation to patient age-based normative results. Patient-specific CLEFT-Q data were also discussed during multidisciplinary cleft and craniofacial team discussions to aid in clinical decision-making. This experience may have applicability to other PRO tools in plastic surgery and other medical specialties where integrating PROs may yield superior patient experience and outcomes.
Optimal Timing for Secondary Reconstruction of Head and Neck Defects after Free Flap Failure
Authors: Gupta Samarth , Goil Pradeep , Mohammad Arbab , Escandón Joseph M.
Published: June 2023

Background:

Finite options exist to address free flap failure. There is a lack of consensus on the standard treatment for secondary reconstruction in such cases. Herein, the authors determined the survival rate of a second flap following a total loss of an initial free flap during head and neck reconstructions and evaluated whether there was a difference in the rate of secondary flap necrosis depending on the timing of reconstruction salvage.

Methods:

The authors retrospectively reviewed 1572 free flaps for head and neck reconstruction from 2010 to 2022. Patients who underwent secondary surgery with flaps after failure of a primary free flap were included. Patients were divided into three groups based on the time for secondary flap reconstruction from the time of primary reconstruction (group A, 0 to 5 days; group B, 6 to 30 days; and group C, >30 days).

Results:

The authors identified 64 cases of complete flap loss after primary reconstruction requiring secondary reconstruction. Pedicled flaps were used in 34.4% of the cases, whereas a second free flap was used in 65.6% of the cases. Overall, the flap failure rate for secondary reconstructions was 6.7% in group A, 35.3% in group B, and 6.7% in group C (P = 0.022). For free tissue transfer, the success rate of a secondary reconstruction was 92.3% in group A, 28.57% in group B, and 93.3% in group C.

Conclusions:

The authors favor an early microsurgical reconstruction (≤5 days) following primary reconstruction in cases of free flap failure. If early reconstruction cannot be performed, a deferred reconstruction with free tissue transfer (>30 days) should be considered.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
The Deciding Factors of Flow Direction in Lymphovenous Anastomosis for Extremity Lymphedema
Authors: Lin Ying-Sheng , Liu Chia-Ju
Published: June 2023

Background:

While using lymphovenous anastomosis (LVA) to treat extremity lymphedema, an antegrade lymphatic to vein flow is usually considered to indicate a functional and effective anastomosis. We analyzed the characteristics of lymphovenous anastomoses in patients with extremity lymphedema to look for the deciding factors of the flow direction.

Patients and Methods:

A total of 45 patients (15 arms and 42 legs) receiving LVA for extremity lymphedema were reviewed. Only the anastomoses with intraoperatively confirmed patent flow or clear visualization of vessel lumens during anastomosis were included for analysis. Multivariate logistic regression was used to identify the contributing factors of intraoperative washout phenomenon or venous reflux.

Results:

A total of 105 eligible LVAs were included for analysis. Anastomosis with a more sclerotic lymphatic duct is statistically significantly associated with more venous reflux (Odds ratio = 2.82, p = 0.003). Larger diameter difference between lymphatic duct and recipient vein (Odds ratio = 12.8, p = 0.02) and less sclerotic lymphatic duct (Odds ratio = 0.47, p = 0.03) are statistically significantly associated with more washout phenomenon.

Conclusion:

The deciding factors of flow direction in LVA are difference of diameters between lymphatic duct and recipient vein, and the severity of lymphosclerosis. To obtain favorable antegrade lymph-to-vein flow, a less sclerotic lymphatic duct with larger diameter and a recipient vein with smaller diameter should be chosen for anastomosis.
Antibiotic Implant Irrigation and Deep Infection: A Retrospective Study of 1508 Patients Undergoing Breast Reconstruction with Implants
Authors: Hemmingsen Mathilde N. , Bennedsen Anne K. , Kullab Randa B. , Weltz Tim K. , Larsen Andreas , Ørholt Mathias , Norlin Caroline Barskov , Kalstrup Julie , Bredgaard Rikke , Sørensen Søren J. , Bjarnsholt Thomas , Hölmich Lisbet R. , Damsgaard Tine E. , Vester-Glowinski Peter , Herly Mikkel
Published: June 2023

Background:

Antibiotic implant irrigation is increasingly used to prevent deep infection after implant-based breast reconstruction. However, there is limited evidence of the clinical effect. In this study, the authors compare the risk of a deep infection in a Danish population of women who received antibiotic implant irrigation with either gentamicin or vancomycin, or no irrigation.

Methods:

The authors retrospectively reviewed consecutive patients undergoing all types of breast reconstruction with implants at Rigshospitalet and Herlev Hospital, Denmark, from 2010 to 2019. Logistic regression was used to compare the risk of deep infection between no irrigation and irrigation with gentamicin or vancomycin, and to account for the difference in risk between patient subgroups and risk factors.

Results:

The authors included 1508 patients who received antibiotic irrigation with gentamicin (500 patients), vancomycin (304 patients), or no irrigation (704 patients). The univariable risk analysis showed a significant decreased risk of deep infection using gentamicin irrigation compared with no irrigation (OR, 0.58; P < 0.05). However, when adjusting for risk factors for infection, there was no significant decrease in the risk of infection when using gentamicin (OR, 0.90; P = 0.71) or vancomycin (OR, 1.0; P = 0.99) compared with the control group.

Conclusions:

The authors found no significant effect of using antibiotic implant irrigation after isolating it from risk factors for deep infection. However, because of the limitations of the study, the authors cannot conclude that there is no effect of antibiotic implant irrigation. There is a need for a randomized, placebo-controlled trial to investigate the effect, and potential side-effects, of antibiotic implant irrigation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Pediatric emergency resuscitative thoracotomy: A Western Trauma Association, Pediatric Trauma Society, and Eastern Association for the Surgery of Trauma collaborative critical decisions algorithm
Authors: Martin Matthew J. , Brasel Karen J. , Brown Carlos V.R. , Hartwell Jennifer L. , de Moya Marc , Inaba Kenji , Ley Eric J. , Moore Ernest E. , Peck Kimberly A. , Rizzo Anne G. , Rosen Nelson G. , Weinberg Jordan A. , Coimbra Raul , Crandall Marie , Mukherjee Kaushik , Ignacio Romeo , Longshore Shannon , Flynn-O’Brien Katherine T. , Ng Grace , Selesner Leigh , Jafri Mubeen
Published: June 2023

LEVEL OF EVIDENCE

Literature synthesis and expert opinion, Level V.
Mental health symptoms and engagement in a stepped-care mental health service among patients with a violent versus nonviolent injury
Authors: O'Connor Kelly E. , Shanholtz Caroline E. , Espeleta Hannah C. , Ridings Leigh E. , Gavrilova Yulia , Hink Ashley , Ruggiero Kenneth J. , Davidson Tatiana M.
Published: June 2023

BACKGROUND

Few studies have examined mental health symptom trajectories and engagement in mental health follow-up in relation to mechanism of injury. This study examined differences in engagement between survivors of nonviolent and violent injury in the Trauma Resilience and Recovery Program (TRRP), a stepped-care, technology-enhanced model that provides evidence-based mental health screening and treatment to patients admitted to our Level I trauma service.

METHODS

This study analyzed data from 2,527 adults enrolled in TRRP at hospital bedside between 2018 and 2022, including 398 patients (16%) with a violent injury and 2,129 patients (84%) with a nonviolent injury. Bivariate and hierarchical logistic regression analyses examined relations between injury type (violent vs. nonviolent) engagement in TRRP and mental health symptoms at 30 day follow-up.

RESULTS

Engagement in services at bedside was similar across survivors of violent and nonviolent traumatic injury. Patients with violent injury had higher levels of posttraumatic stress disorder and depressive symptoms 30 days postinjury but were less likely to engage in mental health screening. Among patients who screened positive for posttraumatic stress disorder and depression, patients with violent injury were more likely to accept treatment referrals.

CONCLUSION

Patients with a violent traumatic injury have higher levels of mental health needs yet face greater barriers to accessing mental health services following their injury relative to those with a nonviolent injury. Effective strategies are needed to ensure continuity of care and access to mental health care to promote resilience and emotional and functional recovery.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Abnormal energy metabolism in ALS: a key player?
Authors: Burg Thibaut , Van Den Bosch Ludo
Published: June 2023

Purpose of the review

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease of the motor system due to the selective and progressive degeneration of both upper and lower motor neurons. Disturbances in energy homeostasis were repeatedly associated with the ALS pathogenesis and appear early during the disease process. In this review, we highlight recent work demonstrating the crucial role of energy metabolism in ALS and discuss its potential clinical relevance.

Recent findings

The alteration of various metabolic pathways contributes to the heterogeneity of the clinical phenotype of ALS. Recent work showed that different ALS mutations selectively impact these pathways and translate to the disease phenotypes in patients and disease models. Strikingly, a growing number of studies point towards an early, even presymptomatic, contribution of abnormal energy homeostasis to the ALS pathogenesis. Advances in metabolomics generated valuable tools to study altered metabolic pathways, to test their therapeutic potential, and to develop personalized medicine. Importantly, recent preclinical studies and clinical trials demonstrated that targeting energy metabolism is a promising therapeutic approach.

Abnormal energy metabolism is a key player in ALS pathogenesis, emerging as a source of potential disease biomarkers and therapeutic targets.
Spring arrival of the common cuckoo at breeding grounds is strongly determined by environmental conditions in tropical Africa
Authors: Davies Jacob G. , Kirkland Máire , Miller Mark G. R. , Pearce-Higgins James W. , Atkinson Philip W. , Hewson Chris M.
Published: June 2023

Failure to adapt migration timing to changes in environmental conditions along migration routes and at breeding locations can result in mismatches across trophic levels, as occurs between the brood parasitic common cuckoo
Cuculus canorus
and its hosts. Using satellite tracking data from 87 male cuckoos across 11 years, we evaluate why the cuckoo has not advanced its arrival to the UK. Across years, breeding ground arrival was primarily determined by timing of departure from stopover in West Africa before northward crossing of the Sahara. Together with high population synchrony and low apparent endogenous control of this event, this suggests that a seasonal ecological constraint operating here limits overall variation in breeding grounds arrival, although this event was itself influenced by carry-over from timing of arrival into tropical Africa. Between-year variation within individuals was, in contrast, mostly determined by northward migration through Europe, probably due to weather conditions. We find evidence of increased mortality risk for (a) early birds following migration periods positively impacting breeding grounds arrival, and (b) late birds, possibly suffering energy limitation, after departure from the breeding grounds. These results help identify areas where demands of responding to global change can potentially be alleviated by improving stopover quality.
Bacterial community dynamics and associated genes in hydrocarbon contaminated soil during bioremediation using brewery spent grain
Authors: Nnadi Mabel Owupele , Bingle Lewis , Thomas Keith
Published: June 2023

Brewery spent grain (BSG) has previously been exploited in bioremediation. However, detailed knowledge of the associated bacterial community dynamics and changes in relevant metabolites and genes over time is limited. This study investigated the bioremediation of diesel contaminated soil amended with BSG. We observed complete degradation of three total petroleum hydrocarbon (TPH C10–C28) fractions in amended treatments as compared to one fraction in the unamended, natural attenuation treatments. The biodegradation rate constant (k) was higher in amended treatments (0.1021k) than in unamended (0.059k), and bacterial colony forming units increased significantly in amended treatments. The degradation compounds observed fitted into the elucidated diesel degradation pathways and quantitative PCR results showed that the gene copy numbers of all three associated degradation genes, alkB, catA and xylE, were significantly higher in amended treatments. High-throughput sequencing of 16S rRNA gene amplicons showed that amendment with BSG enriched autochthonous hydrocarbon degraders. Also, community shifts of the genera

Acinetobacter

and

Pseudomonas

correlated with the abundance of catabolic genes and degradation compounds observed. This study showed that these two genera are present in BSG and thus may be associated with the enhanced biodegradation observed in amended treatments. The results suggest that the combined evaluation of TPH, microbiological, metabolite and genetic analysis provides a useful holistic approach to assessing bioremediation.
Evidence for some antimicrobial properties of English churchyard lichens
Authors: Taylor J. A. , Fourie Toscane , Powell Mark , Chianella Iva
Published: June 2023

The emergence of multidrug-resistant bacteria has driven the need for novel antibiotics. Our investigations have focussed on lichens as they naturally produce a wide range of unique and very effective defence chemicals. The aim of this study was to evaluate some of the antimicrobial properties of ten common British churchyard lichens. The lichen material was sampled from ten species, namely Caloplaca flavescens, Diploicia canescens, Cladonia fimbriata, Psilolechia lucida, Lecanora campestris subsp. Campestris, Lecanora sulphurea, Pertusaria amara f.amara, Lepraria incana, Porpidia tuberculosa and Xanthoria calcicola. Crude acetone extracts of these lichens were tested against six bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonela typhimurium, Listeria monocytogenes and

Lactobacillus acidophilus

) and two fungi (Trichophyton interdigitale and Aspergillus flavus) by the disc-diffusion susceptibility test method. Extracts of Diploicia canescens, Psilolechia lucida, Lecanora sulphurea, Pertusaria amara and Lepraria incana showed clear inhibition of the Gram-positive bacteria tested (S. aureus, L. monocytogenes, L. plantarum). Diploicia canescens, Pertusaria amara and Lepraria incana extracts also inhibited the dermatophyte fungi tested. The Lepraria incana sample tested here was the only extract that showed activity against any of the Gram-negative bacteria tested; it showed inhibition of Pseudomnas aeruginosa. Overall, our results showed that crude extracts of Diploicia canescens and Pertusaria amara had the most potent antimicrobial activity of all the extracts tested. Our results are in general agreement with published findings elsewhere. The activity of the Porpidia tuberculosa margin sample being different from that of the main colony material was an interesting and new finding reported here for the first time.
Bombella pluederhausensis sp. nov., Bombella pollinis sp. nov., Bombella saccharophila sp. nov. and Bombella dulcis sp. nov., four Bombella species isolated from the environment of the western honey bee Apis mellifera
Authors: Härer Luca , Stýblová Sabrina , Ehrmann Matthias A.
Published: June 2023

Four strains of members of the genus

Bombella

were isolated from samples associated with the western honey bee Apis mellifera, which could not be assigned to a species with a validly published name. Strains TMW 2.2543T, TMW 2.2556T, TMW 2.2558T and TMW 2.2559T exhibit in silico DNA–DNA hybridisation (isDDH) and orthologous average nucleotide identity (orthoANI) values below species delineation thresholds compared with all described species of the genus

Bombella

and with each other. TMW 2.2556T and TMW 2.2558T form their own clade within the genus. The major respiratory quinone of all strains was Q-10. The composition of cellular fatty acids was diverse between strains. All strains stained Gram-negative, were rod-shaped, strictly aerobic, pellicle-forming, catalase-positive, oxidase-negative, mesophilic and grew over a wide pH range; they were halosensitive but glucose-tolerant. Unlike the other studied strains, TMW 2.2558T was non-motile. Phylogenetic, chemotaxonomic and physiological analyses revealed a clear distinction between all the strains and species with validly published names. All the data support the proposition of four novel species within the genus

Bombella

, namely Bombella pluederhausensis sp. nov., Bombella pollinis sp. nov., Bombella saccharophila sp. nov. and Bombella dulcis sp. nov., with the respective type strains Bombella pluederhausensis sp. nov. TMW 2.2543T (= DSM 114872T, = LMG 32791T), Bombella pollinis sp. nov. TMW 2.2556T (= DSM 114874T, = LMG 32792T), Bombella saccharophila sp. nov. TMW 2.2558T (= DSM 114875T, = LMG 32793T) and Bombella dulcis sp. nov. TMW 2.2559T (= DSM 114877T, = LMG 32794T). Moreover, three genomes available in the NCBI database that have not yet been described as species with validly published names could be assigned to the proposed species.

Bombella

sp. ESL0378 and

Bombella

sp. ESL0385 to Bombella pollinis sp. nov. and

Bombella

sp. AS1 to Bombella saccharophila sp. nov.
Evaluation and comparison of nine growth- and development-based measures of pubertal timing
Authors: Elhakeem Ahmed , Frysz Monika , Soares Ana G , Bell Joshua A , Cole Tim J , Heron Jon , Howe Laura D , Sebert Sylvain , Tilling Kate , Timpson Nicholas J , Lawlor Deborah A
Published: June 2023

Puberty timing is fundamentally part of life-course health. Yet, little is known about the value of different measures of pubertal timing, particularly in males. We used a population-based cohort to examine nine measures of pubertal age (n=8,500), identifying development of pubic hair in males (12.6y) and breasts in females (11.5y) as early indicators of puberty, and voice breaking (14.2y) and menarche (12.7y) as late indicators. All measures showed evidence of positive phenotypic intercorrelations (e.g., r=0.49: male genitalia and pubic hair ages), and positive genetic intercorrelations. A genetic risk score (GRS) for age at menarche associated positively with all other measures (e.g., difference in female peak height velocity age per SD higher GRS: 0.24y, 95%CI: 0.21 to 0.26), as did GRS for voice breaking age (e.g., difference in male axillary hair age: 0.11y, 0.07 to 0.15). We illustrate the value of different pubertal age measures and their use in life-course research.
Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
Authors: Brunet-Ratnasingham Elsa , Morin Sacha , Randolph Haley E. , Labrecque Marjorie , Bélair Justin , Lima-Barbosa Raphaël , Pagliuzza Amélie , Marchitto Lorie , Hultström Michael , Niessl Julia , Cloutier Rose , Sreng Flores Alina M. , Brassard Nathalie , Benlarbi Mehdi , Prévost Jérémie , Ding Shilei , Anand Sai Priya , Sannier Gérémy , Bareke Eric , Zeberg Hugo , Lipcsey Miklos , Frithiof Robert , Larsson Anders , Zhou Sirui , Nakanishi Tomoko , Morrison David , Vezina Dani , Bourassa Catherine , Gendron-Lepage Gabrielle , Medjahed Halima , Point Floriane , Richard Jonathan , Larochelle Catherine , Prat Alexandre , Arbour Nathalie , Durand Madeleine , Brent Richards J , Moon Kevin , Chomont Nicolas , Finzi Andrés , Tétreault Martine , Barreiro Luis , Wolf Guy , Kaufmann Daniel E.
Published: June 2023

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized COVID-19 patients. Integrated analysis using k-means reveal four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors are delineated by high and low antibody responses. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
BharatSim: An agent-based modelling framework for India
Authors: Cherian Philip , Kshirsagar Jayanta , Neekhra Bhavesh , Deshkar Gaurav , Hayatnagarkar Harshal , Kapoor Kshitij , Kaski Chandrakant , Kathar Ganesh , Khandekar Swapnil , Mookherjee Saurabh , Ninawe Praveen , Noronha Riz Fernando , Ranka Pranjal , Sinha Vaibhhav , Vinod Tina , Yadav Chhaya , Gupta Debayan , Menon Gautam I.
Published: June 2023

BharatSim is an open-source agent-based modelling framework for the Indian population. It can simulate populations at multiple scales, from small communities to states. BharatSim uses a synthetic population created by applying statistical methods and machine learning algorithms to survey data from multiple sources, including the Census of India, the India Human Development Survey, the National Sample Survey, and the Gridded Population of the World. This synthetic population defines individual agents with multiple attributes, among them age, gender, home and work locations, pre-existing health conditions, and socio-economic and employment status. BharatSim’s domain-specific language provides a framework for the simulation of diverse models. Its computational core, coded inScala, supports simulations of a large number of individual agents, up to 50 million. Here, we describe the design and implementation of BharatSim, using it to address three questions motivated by the COVID-19 pandemic in India: (i) When can schools be safely reopened given specified levels of hybrid immunity?, (ii) How do new variants alter disease dynamics in the background of prior infections and vaccinations? and (iii) How can the effects of varied non-pharmaceutical interventions (NPIs) be quantified for a model Indian city? Through its India-specific synthetic population, BharatSim allows disease modellers to address questions unique to this country. It should also find use in the computational social sciences, potentially providing new insights into emergent patterns in social behaviour.

Author summary

Agent-based simulations provide granular ways of describing the dynamics of each individual in a population. Such models are especially useful in describing the spread of an infectious disease, since they can be used to incorporate individual-level heterogeneity in behaviour and susceptibilities, as well as spatio-temporal information. BharatSim is such an agent-based modelling framework for India. It can simulate populations at multiple scales, from a few hundreds to several millions. It creates and uses a predefined synthetic population for India, assimilating it into a simulation framework. The synthetic population defines individuals with multiple attributes, among them age, sex, home, and work locations. We demonstrate the use of BharatSim in three contexts related to the COVID-19 pandemic in India.
The role of BST4 in the pyrenoid ofChlamydomonas reinhardtii
Authors: Adler Liat , Lau Chun Sing , Shaikh Kashif M. , Maldegem Kim A. van , Payne-Dwyer Alex L. , Lefoulon Cecile , Girr Philipp , Atkinson Nicky , Barrett James , Emrich-Mills Tom Z. , Dukic Emilija , Blatt Michael R. , Leake Mark C. , Peltier Gilles , Spetea Cornelia , Burlacot Adrien , McCormick Alistair J. , Mackinder Luke C. M. , Walker Charlotte E.
Published: June 2023

In many eukaryotic algae, CO2 fixation by Rubisco is enhanced by a CO2- concentrating mechanism, which utilizes a Rubisco-rich organelle called the pyrenoid. The pyrenoid is traversed by a network of thylakoid-membranes called pyrenoid tubules, proposed to deliver CO2. In the model algaChlamydomonas reinhardtii(Chlamydomonas), the pyrenoid tubules have been proposed to be tethered to the Rubisco matrix by a bestrophin-like transmembrane protein, BST4. Here, we show that BST4 forms a complex that localizes to the pyrenoid tubules. A Chlamydomonas mutant impaired in the accumulation of BST4 (bst4) formed normal pyrenoid tubules and heterologous expression of BST4 inArabidopsis thalianadid not lead to the incorporation of thylakoids into a reconstituted Rubisco condensate. Chlamydomonasbst4mutant did not show impaired growth at air level CO2. By quantifying the non-photochemical quenching (NPQ) of chlorophyll fluorescence, we show thatbst4displays a transiently lower thylakoid lumenal pH during dark to light transition compared to control strains. When acclimated to high light,bst4had sustained higher NPQ and elevated levels of light-induced H2O2 production. We conclude that BST4 is not a tethering protein, but rather is an ion channel involved in lumenal pH regulation possibly by mediating bicarbonate transport across the pyrenoid tubules.

One-sentence summary

In Chlamydomonas, the pyrenoid-localized bestrophin-like protein BST4 is a putative ion channel involved in pH regulation of the thylakoid lumen, possibly by mediating bicarbonate transport.
Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines
Authors: Reinig Sebastian , Kuo Chin , Wu Chia-Chun , Huang Sheng-Yu , Yu Jau-Song , Shih Shin-Ru
Published: June 2023

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with mRNA vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using LC-MS/MS. Antibody-dependent phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD increased in Medigen-vaccinated individuals after the third dose. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.
The roles of GpsB and DivIVA inStaphylococcus aureusgrowth and division
Authors: Sutton Joshua A. F. , Cooke Mark , Tinajero-Trejo Mariana , Wacnik Katarzyna , Salamaga Bartłomiej , Portman-Ross Callum , Lund Victoria A. , Hobbs Jamie K. , Foster Simon J.
Published: June 2023

The spheroid bacteriumS. aureusis often used as a model of morphogenesis due to its apparent simple cell cycle.S. aureushas many cell division proteins that are conserved across bacteria alluding to common functions. However, despite intensive study we still do not know the roles of many of these components. Here we have examined the functions of the paralogues DivIVA and GpsB in theS. aureuscell cycle. Cells lackinggpsBdisplay a more spherical phenotype than wild type, associated with a decrease in peripheral cell wall peptidoglycan synthesis. This correlates with an increased localisation of penicillin binding proteins at the developing septum, notably PBPs 2 and 3. Our results highlight the role of GpsB as an apparent regulator of cell morphogenesis inS.aureus.
A supermatrix phylogeny of the world’s bees (Hymenoptera: Anthophila)
Authors: Henríquez-Piskulich Patricia , Hugall Andrew F. , Stuart-Fox Devi
Published: June 2023

The increasing availability of large phylogenies has provided new opportunities to study the evolution of species traits, their origins and diversification, and biogeography; yet, with the exception of butterflies, taxonomically well-curated phylogenies are currently lacking for major insect groups. Bees (Hymenoptera: Anthophila) are a large group of insect pollinators that have a worldwide distribution, and a wide variation in ecology, morphology, and life-history traits, including sociality. For these reasons, as well as their major economic importance as pollinators, numerous molecular phylogenetic studies of relationships between and/or within families or genera for this group have been published. We used publicly available sequence data, a family-level phylogenomic backbone, and ultra-conserved element (UCE) data, reconciled to a taxonomic database, to produce a dated phylogeny for bees. The phylogeny comprises 4651 bee species, representing 23% of species and 86% of genera. At family, subfamily, and tribe levels, the data were robust, but between and within some genera relationships remain uncertain. In addition, most of the species with available sequence data are geographically distributed in North America and Europe, highlighting gaps that should be considered in future research to improve our understanding of bee evolution and phylogeography. We provide a summary of the current state of molecular data available and its gaps, and discuss the advantages and limitations of this bee supermatrix phylogeny (available online atbeetreeoflife.org), which may enable new insights into long standing questions about evolutionary drivers in bees, and potentially insects.

Highlights

Bee supermatrix phylogeny constructed with public and published sequence data.

Includes 23% of currently recognised species and covers 86% of genera.

Provides a summary of remaining gaps in bee phylogenetics.

Available online at beetreeoflife.org, with subsetting tool to facilitate comparative analyses.
High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children with and without SARS-CoV-2
Authors: Watkins Timothy A. , Cheemarla Nagarjuna R. , Hänsel Katrin , Green Alex B. , Amat Julien A.R. , Lozano Richard , Dudgeon Sarah N. , Landry Marie L. , Schulz Wade L. , Foxman Ellen F.
Published: June 2023

Recent work indicates that heightened nasal innate immunity in children may impact SARS-CoV-2 pathogenesis. Here, we identified drivers of nasal innate immune activation in children using cytokine profiling and multiplex pathogen detection in 291 pediatric nasopharyngeal samples from the 2022 Omicron surge. Nasal viruses and bacterial pathobionts were highly prevalent, especially in younger children (81% of symptomatic and 37% asymptomatic children overall; 91% and 62% in subjects <5 yrs). For SARS-CoV-2, viral load was highest in young children, and viral load in single infections or combined viral loads in coinfections best predicted nasal CXCL10, a biomarker of the mucosal interferon response. Bacterial pathobionts correlated with high nasal IL-1β and TNF, but not CXCL10, and viral-bacterial coinfections showed a combined immunophenotype. These findings reveal virus and bacteria as drivers of heightened nasal innate immunity in children and suggest that frequent host-pathogen interactions shape responses to respiratory viruses in this age group.
Effective vaccination strategies to control COVID-19 outbreak: A modeling study
Authors: Ko Youngsuk , Peck Kyong Ran , Kim Yae-Jean , Kim Dong-Hyun , Jung Eunok
Published: June 2023

OBJECTIVES

Three years following the start of the COVID-19 pandemic, the World Health Organization (WHO) declared COVID-19 a global health emergency of international concern. As immunity levels in the population acquired through past infections and vaccinations have been decreasing, booster vaccinations have become necessary to control new outbreaks. This study aimed to determine the most suitable vaccination strategy to control the COVID-19 surge.

METHODS

A mathematical model was developed to simultaneously consider the immunity levels induced by vaccines and infections, and employed to analyze the possibility of future resurgence and control using vaccines and antivirals.

RESULTS

As of May 11, 2023, a peak in resurgence is predicted to occur around mid-October of the same year if the current epidemic trend continues without additional vaccinations. In the best scenario, the peak number of severely hospitalized patients can be reduced by 43% (480) compared to the scenario without vaccine intervention (849). Depending on the outbreak trends and vaccination strategies, the best timing for vaccination in terms of minimizing the said peak varies from May to August 2023.

CONCLUSIONS

Our results indicate that if the epidemic continues, the best timing for vaccinations must be earlier than specified by the current plan in Korea. Further monitoring of outbreak trends is crucial for determining the optimal timing of vaccinations to manage future surges.
Sequence features of transcriptional activation domains are consistent with the surfactant mechanism of gene activation
Authors: Broyles Bradley K. , Erkina Tamara Y. , Maris Theodore P. , Gutierrez Andrew T. , Coil Daniel A. , Wagner Thomas M. , Class Caleb A. , Erkine Alexandre M.
Published: June 2023

Transcriptional activation domains (ADs) of gene activators remain enigmatic for decades as they are short, extremely variable in sequence, structurally disordered, and interact fuzzily to a spectrum of targets. We showed that the single required characteristic of the most common acidic ADs is an amphiphilic aromatic–acidic surfactant-like property which is the key for the local gene-promoter chromatin phase transition and the formation of “transcription factory” condensates. We demonstrate that the presence of tryptophan and aspartic acid residues in the AD sequence is sufficient for in vivo functionality, even when present only as a single pair of residues within a 20-amino-acid sequence containing only 18 additional glycine residues. We demonstrate that breaking the amphipathic α-helix in AD by prolines increases AD functionality. The proposed mechanism is paradigm-shifting for gene activation area and generally for biochemistry as it relies on near-stochastic allosteric interactions critical for the key biological function.