bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors for Necrosis after Single Digital Replantation: a Retrospective Analysis of 946 Patients
Authors: Wang Tao , Xiong Fei , Tan Ji Yang , Qiu Yang , Mi Jing-Yi
Published: February 2023

Study design:

A retrospective study

Objective:

Digital necrosis (DN) is a serious complication after replantation. However, predisposing factors, as reported less, remain controversial. The purpose of this study is to explore risk factors of necrosis after single digital replantation.

Methods:

Patients who underwent single digital replantations in our hospital between June. 2014 and October 2020 were included. We regarded DN as the failure group (FG) and digital survive as the success group (SG). The factors were conducted by univariate and multivariate analysis.

Results:

The survival rate in our study was 78.8% (745 of 946). The results of univariate analysis showed that there were significant differences in the levels of D-Dimer (1st), menstrual cycle, injury level, and starting and finishing time of surgery between different groups. In multivariate analysis, age, injury level, duration of surgery, and D-dimer (1 st) were identified as the risk factors for DN in the entire and male population. Additionally, regarding male patients, ischemia time was also found to be a risk factor for DN. In terms of female patients, the menstrual period and menopause were related to DN.

Conclusions:

Many factors, including age, ischemia time, injury level, menstrual period, menopause, and duration of surgery, were related to DN after digital replantation. D-dimer (1 st) was first found as a predicted factor for DN. In addition, these results also showed that the starting and ending times of surgery were associated with DN by univariate analysis. Preoperative measures should be taken to lower the incidence of DN.
Management of the Inferior Alveolar Nerve in Large Sagittal Split Advancements: To Free or Not?
Authors: Massenburg Benjamin B. , Tolley Philip D. , Ettinger Russell E. , Susarla Srinivas M.
Published: February 2023

Purpose:

To evaluate whether neurosensory recovery of the inferior alveolar nerve (IAN) is influenced by its location following sagittal split osteotomy (SSO) in patients undergoing large mandibular movements.

Methods:

This was a prospective, split-mouth study of skeletally mature patients undergoing BSSO. Patients were included as study subjects if they underwent BSSO for mandibular advancement > 10 mm and, following the splits, the IAN was freely entering the distal segment (IANDI) on one side and within the proximal segment (IANPR) on the other. Descriptive, bivariate, and Kaplan-Meier statistics were computed.

Results:

The study sample included 13 subjects (8 female, mean age 18.7 ± 1.8 years) undergoing 26 SSOs. Eleven subjects underwent bimaxillary surgery; 10 had simultaneous genioplasty. The mean mandibular movement was 12.2 ± 1.4 mm and was not significantly different between sides (p = 0.43). All subjects achieved FSR bilaterally within 1 year of surgery. There was no difference in the median times to FSR based upon the location of the IAN (IANDI = 105 days vs IANPR = 126 days, p = 0.57).

Conclusion:

In SSO for mandibular advancement with movements > 10 mm, leaving the IAN within the proximal segment may not impact time to FSR.
Diagnosis and Management of Pseudoblepharoptosis in Eastern Asians: A Commonly Observed But Easily Overlooked Type of Blepharoptosis
Authors: Zhou Xianyu , He Jizhou , Yang Jun , Liu Fei
Published: February 2023

Background:

Pseudoblepharoptosis, which is characterized by ptotic eyelid appearance with normal levator function, is a common abnormality observed in Eastern Asians. Misdiagnosis of pseudoblepharoptosis may lead to inappropriate treatments and unwanted complications. Using the data obtained from a modified levator function examination, this study sought to improve the diagnosis and explore the appropriate treatment of pseudoblepharoptosis based on the typical eyelid anatomy of Eastern Asians.

Methods:

This retrospective study included patients with drooping and bulky eyelids who had been preoperatively diagnosed between January 2018 and December 2018 using a modified approach. Debulking of the retro-orbicularis oculus fat and orbital septum fat and release of the ligament-like structure were performed to correct pseudoblepharoptosis without manipulating the levator muscle. The functional and aesthetic outcomes were evaluated postoperatively.

Results:

The proposed modified approach was significantly more accurate than the traditional technique. Of the patients, 78 (84.8%) and 9 (9.8%) showed good and moderate cosmetic outcomes, respectively. The margin reflex distance 1 value significantly improved from 1.74±0.87 mm preoperatively to 4.56±0.71 mm postoperatively (P<0.05). Moreover, 179 (97.3%) of the 184 eyelids examined achieved adequate correction.

Conclusions:

The modified levator function examination approach used in this study may help improve the diagnosis of pseudoblepharoptosis. Surgical intervention focused on correcting the bulky and drooping upper eyelids and orbital septum may lead to satisfactory outcomes in Eastern Asians with pseudoblepharoptosis without manipulating the levator muscle.
A Novel Preoperative Design to Address Dermatochalasis in Asian Upper Blepharoplasty
Authors: Liu Qing , Wang Zhaohui , Yang Juanmin , Wu Shu , Zhang Youlai , Gan Peidong , Yi Yangyan
Published: February 2023

Background:

The preoperative design for the amount of skin excision of the upper eyelid is a common procedure in Asian blepharoplasty, but there lack of an effective method addressing dermatochalasis to acquire esthetically pleasing results. Our aim was to propose an alternative technique to determine the skin excision combined with the esthetics of eyes for correcting skin laxity and therefore to create attractive double eyelids.

Materials and Methods:

The preoperative invaginating-simulating design combined with esthetic criteria for determining the amount of excised skin were performed during blepharoplasty. The Strasser grading system and the Global Aesthetic Improvement Scale were evaluated by analyzing the preoperative and 6-month-postoperative photographs.

Results:

One hundred forty-two patients were included. The general outline of the “optimal incision” took on a knife in shape with a mean of 2.2±3.32 points of Strasser grading score. A total of 130 of 142 patients (91.5%) were judged as “good results” and 12 of 142 patients (8.5%) were judged as “mediocre”. The Global Aesthetic Improvement Scale showed a significant cosmetic improvement with the result of 89.4%(127 of 142 patients) for “very much improved”, 7.8% for “much improved” and other patients for “improved”. No severe complications were observed.

Conclusions:

This preoperative design approach has been proven to be effective to address dermatochalasis (especially for lateral hooding) by simulating the expected appearance of a double eyelid combined with esthetic criteria of eyes simultaneously, which can contribute to achieving upper-lid rejuvenation and beautiful and natural outcomes.
Perioperative Medication Management in Elective Plastic Surgery Procedures
Authors: Chaya Bachar F. , Rodriguez Colon Ricardo , Boczar Daniel , Daar David , Brydges Hilliard , Thys Erika , Kantar Rami , Saadeh Pierre B.
Published: February 2023

Background:

Perioperative medication management is vital to maintain patient safety while under anesthesia, as well as to avoid postoperative complications. Plastic surgeons make daily decisions on whether to ask a patient to stop taking medication before their surgery. These important decisions can affect bleeding risk, wound healing, and interactions with anesthetics, which can range from minor to life-threatening. Current plastic surgery literature lacks a comprehensive review of perioperative medication management, with existing reports focusing on specific procedures and specific medication classes.

Methods:

A PubMed database search was conducted for articles through July 2021. The bibliographies of included studies were also examined for articles not acquired in the initial search queries. The authors included studies on medication usage and perioperative guidance in patients undergoing elective plastic surgery procedures. The authors excluded studies unrelated to plastic surgery and studies where the medications were used as an intervention. Abstracts, animal studies, studies involving the pediatric population, and book chapters were also excluded, as well as articles not published in English.

Results:

A total of 801 papers were identified by our search terms. After title and abstract screening, 35 papers were selected for full-text review. After full-text review, 20 papers were selected for inclusion, with an additional 6 papers from cited references added. Of the 26 papers, 6 papers discussed psychotropic drugs, 6 papers discussed medications affecting hemostasis, 4 papers discussed hormone-containing medications, 3 papers discussed antilipid medications, 2 papers discussed antihypertensive medications, 2 papers discussed herbal supplements, 1 paper discussed both psychotropic and herbal supplements, 1 paper discussed medications affecting wound healing, and 1 paper discussed rheumatologic medications. A summary of those recommendations was then compiled together.

Conclusions:

The perioperative medication management in elective plastic surgery procedures remains a complex and multidisciplinary process. It is important to manage these patients in a case-by-case manner and to consult a specialist when necessary. Careful medication reconciliation is essential to decrease the likelihood of adverse outcomes and interactions with perioperative anesthetics.
Lung Transplant Outcome From Selected Older Donors (≥70 Years) Equals Younger Donors (<70 Years)
Authors: Vanluyten Cedric , Vandervelde Christelle M. , Vos Robin , Van Slambrouck Jan , Fieuws Steffen , De Leyn Paul , Nafteux Philippe , Decaluwé Herbert , Van Veer Hans , Depypere Lieven , Jansen Yanina , Provoost An-Lies , Neyrinck Arne P. , Ingels Catherine , Vanaudenaerde Bart M. , Godinas Laurent , Dupont Lieven J. , Verleden Geert M. , Van Raemdonck Dirk , Ceulemans Laurens J.
Published: February 2023

Objective:

To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years.

Background:

Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited.

Methods:

All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed.

Results:

Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70–84 years) versus 49 years (range: 12–69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients (P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications (P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% (P = 0.72) and 51.5% versus 59.2% (P = 0.41), respectively.

Conclusions:

LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).
Magnetic Resonance Imaging Predictors of Hepatocellular Carcinoma Progression and Dropout in Patients in Liver Transplantation Waiting List
Authors: Baghdadi Azarakhsh , Luu Harry T. , Shaghaghi Mohammadreza , Ghadimi Maryam , Simsek Cem , Xu Ziyi , Hazhirkarzar Bita , Motaghi Mina , Hammami Muhammad , Clark Jeanne M. , Gurakar Ahmet , Kamel Ihab R. , Kim Amy K.
Published: February 2023

Background.

With the rising incidence of hepatocellular carcinoma (HCC), more patients are now eligible for liver transplantation. Consequently, HCC progression and dropout from the waiting list are also anticipated to rise. We developed a predictive model based on radiographic features and alpha-fetoprotein to identify high-risk patients.

Methods.

This is a case-cohort retrospective study of 76 patients with HCC who were listed for liver transplantation with subsequent liver transplantation or delisting due to HCC progression. We analyzed imaging-based predictive variables including tumor margin (well- versus ill-defined), capsule bulging lesions, volumetric analysis and distance to portal vein, tumor numbers, and tumor diameter. Volumetric analysis of the index lesions was used to quantify index tumor total volume and volumetric enhancement, whereas logistic regression and receiver operating characteristic curve (ROC) analyses were used to predict the main outcome of disease progression.

Results.

In univariate analyses, the following baseline variables were significantly associated with disease progression: size and number of lesions, sum of lesion diameters, lesions bulging the capsule, and total and venous-enhancing (viable) tumor volumes. Based on multivariable analyses, a risk model including lesion numbers and diameter, capsule bulging, tumor margin (infiltrative versus well-defined), and alpha-fetoprotein was developed to predict HCC progression and dropout. The model has an area under the ROC of 82%, which was significantly higher than Milan criteria that has an area under the ROC of 67%.

Conclusions.

Our model has a high predictive test for patient dropout due to HCC progression. This model can identify high-risk patients who may benefit from more aggressive HCC treatment early after diagnosis to prevent dropout due to such disease progression.
Application of Ex Vivo Normothermic Machine Perfusion in Deceased Donors With Acute Kidney Injury With Successful Renal Transplantation: A Preliminary Experience
Authors: Choudhary Devprakash , Sharma Ashish , Singh Sarbpreet , Kenwar Deepesh B. , Walker Minz Ranjana , Singh Kohli Harbir , Nada Ritambhra , Wangkheimayum Sujata , Jain Kajal , Patil Shivakumar S.
Published: February 2023

Background.

Ex vivo normothermic machine perfusion (NMP) has improved organ preservation and viability assessment among heart, liver, and lung transplantation. However, literature regarding the application of NMP in human clinical kidney transplantation remains limited. Numerous kidneys, especially from donors with stage 3 acute kidney injury (AKI), are not utilized concerning the high rate of delayed graft function (DGF) and primary nonfunction. The present study investigated the impact of NMP (135–150 min) on short-term outcomes after kidney transplantation from deceased donors with AKI.

Methods.

Graft outcomes of NMP kidneys were compared with contralateral kidneys stored in static cold storage (SCS) from the same donor with AKI during December 2019–June 2021. The study’s primary aim is to assess the safety and feasibility of NMP in deceased donors with AKI. The primary outcome was DGF. Secondary outcomes were duration of DGF, biopsy-proven rejection, postoperative intrarenal resistive index, postoperative infections, hospital stay duration, primary nonfunction, and kidney function estimated glomerular filtrate rate at discharge, 3 mo, and 1 y.

Results.

Five pairs of AKI kidneys (NMP versus SCS) were included in the final analysis. The results show no statistically significant differences in clinical outcomes between NMP versus SCS kidneys; however, NMP kidneys demonstrated slightly improved estimated glomerular filtrate rate at 3 mo (59.8 ± 5.93 [59] versus 75.20 ± 14.94 [74]) mL/min/1.73 m2 (P < 0.065) and at the last follow-up (12–29 mo) (72.80 ± 10.71 [75]) versus (94 ± 22.67 [82]) mL/min/1.73 m2 (P < 0.059) as compared with SCS kidneys. A higher proportion of NMP kidneys had normal intrarenal resistive index (0.5–0.7) and mild acute tubular injury on protocol biopsy, suggesting NMP is safe and feasible in deceased donors with acute kidney injury.

Conclusions.

NMPs of AKI donor kidneys are safe and feasible. A larger cohort is required to explore the reconditioning effect of NMP on AKI kidneys.
Comparison of the Immune Response After an Extended Primary Series of COVID-19 Vaccination in Kidney Transplant Recipients Receiving Standard Versus Mycophenolic Acid–sparing Immunosuppressive Regimen
Authors: Phirom Supitchaya , Phannajit Jeerath , Jantarabenjakul Watsamon , Paitoonpong Leilani , Kitrungphaiboon Thidarat , Choktaweesak Nuchjarnun , Kupatawintu Pawinee , Wattanatorn Salin , Prasithsirikul Wisit , Eiam-Ong Somchai , Avihingsanon Yingyos , Hansasuta Pokrath , Vanichanan Jakapat , Townamchai Natavudh
Published: February 2023

Background.

Two doses of coronavirus disease 2019 vaccination provide suboptimal immune response in transplant patients. Mycophenolic acid (MPA) is one of the most important factors that blunts the immune response. We studied the immune response to the extended primary series of 2 doses of AZD1222 and a single dose of BNT162b2 in kidney transplant patients who were on the standard immunosuppressive regimen compared to those on the MPA-sparing regimen.

Methods.

The kidney transplant recipients who were enrolled into the study were divided into 2 groups based on their immunosuppressive regimen. Those on the standard immunosuppressive regimen received tacrolimus (TAC), MPA, and prednisolone (standard group). The patients in the MPA-sparing group received mammalian target of rapamycin inhibitors (mTORi) with low dose TAC plus prednisolone (MPA-sparing group). The vaccination consisted of 2 doses of AZD1222 and a single dose of BNT162b2.

Results.

A total of 115 patients completed the study. There were 76 (66.08%) patients in the standard group and 39 (33.91%) patients in the MPA-sparing group. The overall median anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S antibody level at 4 wk after vaccine completion was 676.64 (interquartile range = 6.02–3644.03) BAU/mL with an 80% seroconversion rate. The MPA-sparing group achieved higher anti–SARS-CoV-2 S antibody level compared to the standard group (3060.69 and 113.91 BAU/mL, P < 0.001). The seroconversion rate of MPA-sparing and standard groups were 97.4% and 71.1%, respectively (P < 0.001). The anti-HLA antibodies did not significantly increase after vaccination.

Conclusions.

The extended primary series of 2 doses of AZD1222 and a single dose of BNT162b2 provided significant humoral immune response. The MPA-sparing regimen with mTORi and low dose TAC had a higher ant–SARS-CoV-2 S antibody level and seroconversion rate compared to the participants in the standard regimen.
Seizure Occurring During Baclofen Monotherapy for Phenibut Withdrawal
Authors: Patt Amber , Fox Haley , Wells Lauren , Theobald Jillian , Feldman Ryan
Published: February 2023

Objective

Phenibut is a widely available gamma-aminobutyric acid B receptor agonist. When taken chronically, phenibut causes dependence and subsequent withdrawal if stopped. Baclofen, a gamma-aminobutyric acid B receptor agonist structurally related to phenibut, has been used to manage phenibut withdrawal (PW), although baclofen doses for PW are not well defined and may exceed Food and Drug Administration–approved doses. Little data described outcomes from baclofen use.

Methods

This case details a patient who experienced a seizure while on baclofen 10 mg thrice daily as monotherapy for PW and highlights a potential risk of underdosing baclofen as monotherapy in the management of PW.

Results

A man in his early 30s with anxiety, depression, and substance use disorder presented to the emergency department by family for lethargy and confusion starting earlier that day. He had been using 25–30 g of phenibut daily for the past 6 months. On arrival, he was hypertensive, tachycardic, tachypneic, and lethargic. The patient received 1 mg of intravenous lorazepam and was admitted to the hospital for presumed PW. His symptoms improved overnight, and he was discharged on 10 mg of baclofen thrice daily. He returned 28 hours later after having a seizure and required intensive care admission in addition to multimodal drug therapy.

Conclusions

Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.
Knowing When to Ignore the Numbers: Single Center Experience Transplanting Deceased Donor Kidneys with Poor Perfusion Parameters
Authors: Werenski Hope , Stratta Robert J , Sharda Berjesh , Garner Matthew , Farney Alan C , Orlando Giuseppe , McCracken Emily , Jay Colleen L
Published: February 2023

Background:

Hypothermic machine perfusion is frequently utilized in evaluating marginal kidneys, with poor perfusion parameters (PPP) contributing to delays in kidney placement or discard. We examined outcomes in deceased donor kidney transplants (DDKT) with PPP compared to those with optimal perfusion parameters (OPP).

Study Design:

We conducted a retrospective single center cohort study from 2001 to 2021 comparing PPP (n=91) to OPP (n=598) DDKT. PPP was defined as terminal flow ≤80 ml/min AND terminal resistance ≥0.40 mmHg/ml/min. OPP was defined as terminal flow ≥120 ml/min AND terminal resistance ≤0.20 mmHg/ml/min.

Results:

Mean terminal flow was PPP 66 ± 16 vs OPP 149 ± 21 ml/min and resistance was PPP 0.47 ± 0.10 vs OPP 0.15 ± 0.04 mmHg/ml/min (both p<0.001). Donor age, donation after cardiac death, and terminal serum creatinine levels were similar between groups. Mean Kidney Donor Profile Index (KDPI) was higher among PPP donors (PPP 65 ± 23% vs OPP 52 ± 27%, p<0.001). The PPP transplant group had more females and lower weight and BMI. Delayed graft function was comparable (PPP 32% vs OPP 27%, p=0.33) even though cold ischemia times (CIT) trended toward longer in PPP kidneys (PPP 28 ± 10 vs OPP 26 ± 9 hours, p=0.09). One-year patient survival (PPP 98% vs OPP 97%, p=0.84) and graft survival (PPP 91% vs OPP 92%, p=0.23) were equivalent. PPP did predict inferior overall and death-censored graft survival long-term (overall HR=1.63, 95%CI=1.19-2.23 and death-censored HR=1.77, 95%CI=1.15-2.74). At 1 year, eGFR was higher with OPP kidneys (PPP 40 ± 17 vs OPP 52 ± 19 ml/min/1.73m2, p<0.001).

Conclusion:

Short-term outcomes in PPP kidneys were comparable to OPP kidneys despite higher KDPI and longer CIT, suggesting a role for increased utilization of these organs with careful recipient selection.
Synergistic antimicrobial effect of ascorbic acid and nicotinamide with rifampicin and vancomycin against SCCmec type IV methicillin-resistant Staphylococcus aureus (MRSA)
Authors: AlSaleh Abdullah , Shahid Mohammed , Farid Eman , Kamal Nermin , Bindayna Khalid
Published: February 2023

Background. Methicillin-resistant

Staphylococcus aureus

(MRSA) is a pathogenic bacteria involved in a wide spectrum of human diseases. Many virulence factors promote this widespread propagation. One important factor is acquiring antibiotic resistance genes, which leads to a reduction in the availability and efficacy of therapy options. Recently, research has suggested that the remarkable antimicrobial effect of antioxidants against superbugs such as MRSA shows synergistic effects when accompanied by antimicrobial therapy. This paper aims to examine the synergistic effects of ascorbic acid and nicotinamide with a panel of antibiotics used in antimicrobial therapy against MRSA.

Material and Methods. Two SCCmec type IV MRSA reference strains (EMRSA-15 and USA300) and 10 MRSA clinical isolates feature in this paper. SCCmec typing was conducted on the 10 clinical isolates via multiplex PCR after identification. Synergy experiments on antioxidants and antibiotics were evaluated via checkerboard assay. The minimum inhibitory concentration (MIC) of each agent was determined in accordance with the Clinical and Laboratory Standards Institute (CLSI) M100 guidelines through twofold microdilution assay.

Results and Discussion. Synergy (FIC <0.5) was demonstrated for ascorbic acid (1/2 to 1/4 MIC) with rifampicin (1/2 to 1/8 MIC), and also ascorbic acid (1/2 to 1/16 MIC) when associated with vancomycin (1/2 MIC). Similarly, nicotinamide (1/2 to 1/16 MIC) showed a synergistic effect when paired with low concentrations of rifampicin (1/2 to 1/16 MIC), and also (at 1/4 to 1/16 MIC) with vancomycin (1/2 MIC). All reduced MICs due to synergistic combinations demonstrated statistical significance (P<0.05).

Conclusion. The synergistic activity demonstrated in associating antioxidants with antibiotics shows promise in managing superbugs. However, more research is required to better understand the mechanism of the synergy and for utilization in clinical care.
Sulfurospirillum diekertiae sp. nov., a tetrachloroethene-respiring bacterium isolated from contaminated soil
Authors: Jin Huijuan , Huo Leitao , Yang Yi , Lv Yan , Wang Jingjing , Maillard Julien , Holliger Christof , Löffler Frank E. , Yan Jun
Published: February 2023

Two anaerobic, tetrachloroethene- (PCE-) respiring bacterial isolates, designated strain ACSDCE
T and strain ACSTCE, were characterized using a polyphasic approach. Cells were Gram-stain-negative, motile, non-spore-forming and shared a vibrioid- to spirillum-shaped morphology. Optimum growth occurred at 30 °C and 0.1–0.4 % salinity. The pH range for growth was pH 5.5–7.5, with an optimum at pH 7.2. Hydrogen, formate, pyruvate and lactate as electron donors supported respiratory reductive dechlorination of PCE to cis-1,2-dichloroethene (cDCE) in strain ACSDCE
T and of PCE to trichloroethene (TCE) in strain ACSTCE. Both strains were able to grow with pyruvate under microaerobic conditions. Nitrate, elemental sulphur, and thiosulphate were alternative electron acceptors. Autotrophic growth was not observed and acetate served as carbon source for both strains. The major cellular fatty acids were C16 : 1
 ω7c, C16 : 0, C14 : 0 and C18 : 1
 ω7c. Both genomes feature a circular plasmid. Strains ACSDCE
T and ACSTCE were previously assigned to the candidate species 'Sulfurospirillum acididehalogenans'. Here, based on key genomic features and pairwise comparisons of whole-genome sequences, including average nucleotide identity, digital DNA–DNA hybridization and average amino acid identity, strains ACSDCE
T and ACSTCE, 'Ca. Sulfurospirillum diekertiae' strains SL2-1 and SL2-2, and the unclassified

Sulfurospirillum

sp. strain SPD-1 are grouped into one distinct species separate from previously described

Sulfurospirillum

species. Compared to

Sulfurospirillum multivorans

and

Sulfurospirillum halorespirans

, which dechlorinate PCE to cDCE without substantial TCE accumulation, these five strains produce TCE or cDCE as the end product. In addition, some cellular fatty acids (e.g., C16 : 0 3OH, C17 : 0 iso 3OH, C17 : 0 2OH) were detected in strains ACSDCE
T and ACSTCE but not in other

Sulfurospirillum

species. On the basis of phylogenetic, physiological and phenotypic characteristics, 'Ca. Sulfurospirillum acididehalogenans' and 'Ca. Sulfurospirillum diekertiae' are proposed to be merged into one novel species within the genus

Sulfurospirillum

, for which the name

Sulfurospirillum diekertiae

sp. nov. is proposed. The type strain is ACSDCE
T (=JCM 33349T= KCTC 15819T=CGMCC 1.5292T).
Identification of rare missense variants reducing cathepsin O secretion in families with intracranial aneurysm
Authors: Freneau Milène , Blanchet Raphael , Benichi Sandro , Mrad Mary-Adel , Batta Surya Prakash Rao , Rio Marc , Bonnaud Stéphanie , Lindenbaum Pierre , Laporte Fabien , Cuénot Stéphane , Quillard Thibaud , Morel Sandrine , Kwak Brenda R. , Bijlenga Philippe , Deleuze Jean-François , Dina Christian , Bodet Maxence , Chatel Stéphanie , Bourcereau Emmanuelle , Jouan Solène , Consoli Arturo , Dargazanli Cyril , Ognard Julien ,   ICAN Study Group, Desal Hubert , Vion Anne-Clémence , Bourcier Romain , Loirand Gervaise , Redon Richard
Published: February 2023

Intracranial aneurysm (IA) is a common cerebrovascular abnormality characterized by localized dilation and wall thinning in intracranial arteries, which can rupture and lead to fatal subarachnoid hemorrhage. Although the pathophysiology of IA remains largely unknown, increasing evidence suggests that genetic susceptibility plays a predominant role. Here, we combined whole exome sequencing and identity-by-descent analyses with functional investigations to identify rare functional variants associated to IA in families with multiple affected subjects. We identified two rare missense variants in theCTSOgene in two large pedigrees. We found that the cysteine-type papain-like cathepsin O (CTSO) encoded byCTSOis expressed in the wall of human IA domes. Stretching of vascular smooth muscle cells (VSMC) induced secretion of CTSO, which acted as an extracellular protease controlling VSMC migration and adhesion to the extracellular matrix. CTSO depletion, as well as expression of the two CTSO variants, which are poorly secreted, increased the amount of fibronectin. In addition, CTSO depletion increased VSMC stiffness, which was reduced by the addition of exogenous CTSO. Collectively, our findings identify CTSO as a potential new player in arterial remodeling, regulating fibronectin deposition and VSMC function, supporting the causal role of rare codingCTSOvariants in familial forms of IA.
Evaluation of statistical detection of change algorithm for triaging multiple sclerosis patients with new lesion activity on longitudinal brain MRI
Authors: Homssi Moayad , Sweeney Elizabeth M. , Demmon Emily , Mannheim William , Sakirsky Michael , Wang Yi , Gauthier Susan A. , Gupta Ajay , Nguyen Thanh D.
Published: February 2023

Background and Purpose

Identification of new MS lesions on longitudinal MRI by human readers is time-consuming and prone to error. Our objective was to evaluate the improvement in a subject-level detection performance by readers when assisted by the automated statistical detection of change (SDC) algorithm.

Materials and Methods

A total of 200 MS patients with mean inter-scan interval of 13.2 ± 2.4 months were included. SDC was applied to the baseline and follow-up FLAIR images to detect potential new lesions for confirmation by readers (Reader+SDC method). This method was compared with readers operating in the clinical workflow (Reader method) for a subject-level detection of new lesions.

Results

Reader+SDC found 30 subjects (15.0%) with at least one new lesion, while Reader detected 16 subjects (8.0%). As a subject-level triage tool, SDC achieved a perfect sensitivity of 1.00 (95% CI: [0.88, 1.00]) and a moderate specificity of 0.67 (95% CI: [0.59, 0.74]). The agreement on a subject-level was 0.91 (95% CI: [0.87, 0.95]) between Reader+SDC and Reader, and 0.72 (95% CI: [0.66, 0.78]) between Reader+SDC and SDC.

Conclusion

SDC improves the detection accuracy of human readers and can serve as a time-saving patient triage tool for detecting new MS lesion activity on longitudinal FLAIR images.
Clinical Characteristics and Long-term Symptomology of Post-COVID-19 Olfactory and Gustatory Dysfunction
Authors: Boyd Amelia , Minichetti Dante , Lemire Evan , Haber Adam L , Roditi Rachel E , Laidlaw Tanya , Bankova Lora
Published: February 2023

Olfactory and gustatory dysfunction persists in 2-4% of patients who have recovered from COVID-19 beyond 6 months. Dysosmia (distorted smell) and dysgeusia (distorted taste) are frequently observed in the acute phase of many upper respiratory viral infections. However, persistent dysosmia in these patients is associated with persistent nasal inflammation. The purpose of this study was to determine the extent of patient self-assessed post-COVID-19 olfactory and gustatory dysfunction and to understand the quality and severity of the subjective symptoms over a year. A total of 426 registry participants were recruited to complete initial online questionnaires and follow up at three post-enrollment time points: 3 months, 6 months, 12 months. The Registry questionnaires assessed nasal inflammation (Sino-Nasal Outcome Test - SNOT-22), mental health (The Patient Health Questionnaire-2 -PHQ-2; Neuro-QoL Positive Affect and Well-Being - PAW-23), sleep quality (The Pittsburgh Sleep Quality Index – PSQI), In a cohort of 74 patients, clinical measurements of smell (Smell Identification Test (UPSIT) and taste (Waterless Taste Test (B-WETT)) were performed to validate self-reported measures of sensory impairment. Our data indicate that persistent COVID-19 olfactory and gustatory dysfunction is not associated with subjective measures of nasal inflammation. However, dryness of the nose/mouth, mood disturbance, and poor sleep quality are reported by the majority of participants. Participants struggle with detecting specific foul/dangerous odorants and tasting subtle flavors, which could have a negative effect on patient safety and well-being. Those infected during the earlier waves of the pandemic have more persistent and severe symptoms. Objective measure of both smell and taste are significantly reduced in the majority of participants with self-reported olfactory and gustatory dysfunction. Finally, standard anti-inflammatory topical and systemic therapy does not improve the subjective sense of smell while olfactory training is marginally more effective. This establishes persistent COVID19 olfactory and gustatory dysfunction as a chronic and difficult to treat syndrome resistant to standard anti-inflammatory therapy.
Characterisation of the neonatal brain using myelin-sensitive magnetisation transfer imaging
Authors: Blesa Cábeza Manuel , Vaher Kadi , York Elizabeth N. , Galdi Paola , Sullivan Gemma , Stoye David Q. , Hall Jill , Corrigan Amy E. , Quigley Alan J. , Waldman Adam D. , Bastin Mark E. , Thrippleton Michael J. , Boardman James P.
Published: February 2023

A cardinal feature of the encephalopathy of prematurity is dysmaturation of developing white matter and subsequent hypomyelination. Magnetisation transfer imaging (MTI) offers surrogate markers for myelination including magnetisation transfer ratio (MTR) and magnetisation transfer saturation (MTsat). Using data from 105 neonates, we characterise MTR and MTsat in the developing brain and investigate how these markers are affected by gestational age at scan and preterm birth. We explore correlations of the two measures with fractional anisotropy (FA), radial diffusivity (RD) and T1w/T2w ratio which are commonly used markers of white matter integrity in early life. We used two complementary analysis methods: voxel-wise analysis across the white matter skeleton, and tract-of-interest analysis across 16 major white matter tracts. We found that MTR and MTsat positively correlate with gestational age at scan. Preterm infants at term-equivalent age had lower values of MTsat in the genu and splenium of the corpus callosum, while MTR was higher in central white matter regions, the corticospinal tract and the uncinate fasciculus. Correlations of MTI metrics with other MRI parameters revealed that there were moderate positive correlations between T1w/T2w and MTsat and MTR at voxel-level, but at tract-level FA had stronger positive correlations with these metrics. RD had the strongest correlations with MTI metrics, particularly with MTsat in major white matter tracts. The observed changes in MTI metrics are consistent with an increase in myelin density during early postnatal life, and lower myelination and cellular/axonal density in preterm infants at term-equivalent age compared to term controls. Furthermore, correlations between MTI-derived features and conventional measures from dMRI provide new understanding about the contribution of myelination to non-specific imaging metrics that are often used to characterise early brain development.
Gender and ethnicity intersect to reduce participation at a large European Hybrid HIV Conference
Authors: Howe A. , Wan YI. , Gilleece Y , Aebi-Popp K , Dhairyawan R , Bhagani S , Paparini S. , Orkin C.
Published: February 2023

Introduction

The negative effect of female gender identity on participation at face-to-face academic conferences for delegates, speakers, chairs and panellists has previously been reported. Little is known about how ethnicity may affect conference participation, or about how gender and ethnicity intersect. To our knowledge, this is the first study describing conference participation by both ethnicity and gender in panellists and delegates, and the first to describe this within a hybrid conference setting.

Methods

We collaborated with the European AIDS Clinical Society (EACS), the organisers of the 18th European AIDS Conference, a large, 3223 delegate, hybrid conference held online and in London, over four days in October 2021. During the conference, we observed the number and type of questions asked at 12 of 69 sessions and described characteristics of the panel composition by ethnicity, gender and seniority. A post-conference survey of conference attendees collated demographic information, number of questions asked during the conference and the reasons for not asking questions.

Results

Men asked the most questions and were more likely to ask multiple questions in the observed sessions (61.5%). People from White ethnic groups asked >95% of the questions in the observed sessions. The fewest questions were asked in the sessions with the least diverse panels in terms of both ethnicity and gender. Barriers to asking questions differed between genders and ethnicities.

Conclusions

Improvement in access and participation at medical conferences is needed. Our study aims to raise awareness and provide evidence to help improve equality, diversity and inclusion in the professional medical conference setting and support equitable dissemination and sharing of knowledge. Intersections of gender and ethnicity shape inequality and need to be examined in combination. Further work is needed to evaluate the role of other social identities. We recommend future work takes such intersectionality into account and that conference organisers strive for diversity on panels to improve education and engagement of delegates.
Population mobility and the development of Botswana’s generalized HIV epidemic: a network analysis
Authors: Song Janet , Okano Justin T. , Ponce Joan , Busang Lesego , Seipone Khumo , Valdano Eugenio , Blower Sally
Published: February 2023

The majority of people with HIV live in sub-Saharan Africa, where HIV epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, population-level mobility has not yet been studied in the context of the development of generalized HIV epidemics. Here we do so by studying historical migration data from Botswana which has one of the most severe generalized HIV epidemics worldwide; in 2021, HIV prevalence was 21%. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana’s epidemic, the population was highly mobile and there were substantial urban-to-rural and rural-to-urban migratory flows. We test this hypothesis by conducting a network analysis using a historical time series (1981 to 2011) of micro-census data from Botswana. We found 10% of the population moved their residency annually, complex migration networks connected urban with rural areas, and there were very high rates of rural-to-urban migration. Notably, we also found mining towns were both important in-flow and out-flow migration hubs; consequently, there was a very high turnover of residents in towns. Our results support our hypothesis, and together, provide one explanation for the development of Botswana’s generalized epidemic.
Influence of autozygosity on common disease risk across the phenotypic spectrum
Authors: Malawsky Daniel S. , van Walree Eva , Jacobs Benjamin M , Heng Teng Hiang , Huang Qin Qin , Sabir Ataf H. , Rahman Saadia , Sharif Saghira Malik , Khan Ahsan , Mirkov Maša Umićević ,   23andMe Research Team,   Genes & Health Research Team, Posthuma Danielle , Newman William G. , Griffiths Christopher J. , Mathur Rohini , van Heel David A. , Finer Sarah , O’Connell Jared , Martin Hilary C.
Published: February 2023

Autozygosity is associated with rare Mendelian disorders and clinically-relevant quantitative traits. We investigated associations between FROH(fraction of the genome in runs of homozygosity) and common diseases in Genes & Health (N=23,978 British South Asians), UK Biobank (N=397,184), and 23andMe, Inc. We show that restricting analysis to offspring of first cousins is an effective way of removing confounding due to social/environmental correlates of FROH. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROHand twelve common diseases. We replicated the associations with type 2 diabetes (T2D) and post-traumatic stress disorder via between-sibling analysis in 23andMe (median N=480,282). We estimated that autozygosity due to consanguinity accounts for 5-18% of T2D cases amongst British Pakistanis. Our work highlights the possibility of widespread non-additive effects on common diseases and has important implications for global populations with high rates of consanguinity.
Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants
Authors: Gonzalez Veronica , Li Lin , Buarpung Sirirak , Prahl Mary , Robinson Joshua F. , Gaw Stephanie L.
Published: February 2023

Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human villous explant model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure.
FPsim: An agent-based model of family planning
Authors: O’Brien Michelle L. , Valente Annie , Kerr Cliff C. , Proctor Joshua L. , Noori Navideh , Root Elisabeth D. , Olsen Helen , Buxton Samuel , Chabot-Couture Guillaume , Klein Daniel J. , Zimmermann Marita
Published: February 2023

The biological and behavioral underpinnings of family planning (FP) unfold on an individual level, across a full reproductive life course, and within a complex system of social and structural constraints. Yet, much of the existing FP modeling landscape has focused solely on macro- or population-level dynamics of family planning. There is a need for an individual-based approach to provide a deeper understanding of how family planning is intertwined with individuals’ lives and health at the micro-level, which can contribute to more effective, person-centered design of both contraceptive technologies and programmatic interventions. This article introduces the Family Planning Simulator (FPsim), a data-driven, agent-based model of family planning, which explicitly models individual heterogeneity in biology and behavior over the life course. Agents in FPsim can experience a wide range of life-course events, such as increases in fecundability (and primary infertility), sexual debut, contraceptive choice, postpartum family planning, abortion, miscarriage, stillbirth, infant mortality, and maternal mortality. The core components of the model – fecundability and contraceptive choice, are represented individually and probabilistically, following age-specific patterns observed in demographic data and prospective cohort studies. Once calibrated to a setting leveraging multiple sources of data, FPsim can be used to build hypothetical scenarios and interrogate counterfactual research questions about the use, non-use, and/or efficacy of family planning programs and contraceptive methods. To our knowledge, FPsim is the first open-source, individual-level, woman-centered model of family planning.

Author Summary

Although the causes and consequences of family planning unfold on an individual level, few models of family planning consider individual heterogeneity over the life course. To that end, we introduce the methodology, parameters, and use-case(s) of the family planning simulator (FPsim). FPsim is a data-driven agent-based model of family planning, which explicitly models individual heterogeneity in biology and behaviors over a woman’s full life course to better understand the micro-level dynamics leading to more or less successful family planning programs and policies. FPsim is a data-driven model that leverages multiple sources of data to simulate realistic populations in settings that reflect real-life contexts. It is designed to be flexible and user-friendly, allowing for custom calibrations and providing integrated functions for straightforward use. This manuscript describes the model design, including its parameters, potential data sources, and limitations. We illustrate the functionality of FPsim using hypothetical scenarios that improve upon existing injectable contraceptives and introduce new injectable contraceptives into a Senegal-like setting.
Lessons Learned from Health Coverage Expansion in Massachusetts: Primary Care for Individuals with Serious Psychiatric Illness: Pre- and Post- 2006 Coverage Mandates
Authors: Murphy Beth L. , Mellen Emily , Hodgkin Dominic , Doonan Michael T. , Cohen Bruce M.
Published: February 2023

Purpose

Improved access to care, particularly primary care, is a key goal of healthcare reform proposals. Individuals with severe psychiatric illness have high rates of emergency room use rather than primary/preventive care. Massachusetts implemented health care reform in 2006 intended to provide more individuals with health care insurance and, thereby, access to primary care. To our knowledge no study has assessed whether this legislation impacted barriers to primary care access among individuals with serious mental illness.

Methods

This study looked at effects of the 2006 Massachusetts legislation among individuals being hospitalized at a large psychiatric hospital drawing patients from throughout Eastern Massachusetts. A retrospective review of records noted whether a primary care physician was identified, along with demographic and clinical characteristics for each patient.

Results

Primary care affiliation was significantly lower in 2008 than 2005. Affiliation increased 9 years after legislation, though not to the levels of the year prior to the legislation. Risk ratios for PCP non-affiliation were similar whether the model controlled for demographic characteristics only; primary and drug and alcohol related diagnoses in addition to demographic characteristics; or insurance type in addition to demographic characteristics and diagnoses.

Conclusions

The risk of being unaffiliated with a PCP 2 years after legislative reform was nearly 20% higher than 1 year before. Our findings are concerning in that patients at this large regional psychiatry hospital may have been receiving less primary/preventive care in 2008 than in 2005, despite legislation aimed at improving primary care access for the general population.