bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of subsequent vertebral compression fractures after thoracolumbar kyphoplasty: a multicenter retrospective analysis
Authors: Yu Weibo , Zhang Haiyan , Yao Zhensong , Zhong Yuanming , Jiang Xiaobing , Cai Daozhang
Published: April 2023

Objective

Second fractures at the cemented vertebrae (SFCV) are often seen after percutaneous kyphoplasty, especially at the thoracolumbar junction. Our study aimed to develop and validate a preoperative clinical prediction model for predicting SFCV.

Methods

A cohort of 224 patients with single-level thoracolumbar osteoporotic vertebral fractures (T11–L2) from 3 medical centers was analyzed between January 2017 and June 2020 to derive a preoperative clinical prediction model for SFCV. Backward-stepwise selection was used to select preoperative predictors. We assigned a score to each selected variable and developed the SFCV scoring system. Internal validation and calibration were conducted for the SFCV score.

Results

Among the 224 patients included, 58 had postoperative SFCV (25.9%). The following preoperative measures on multivariable analysis were summarized in the 5-point SFCV score: bone mineral density (≤–3.05), serum 25-hydroxy vitamin D3 (≤17.55 ng/mL), standardized signal intensity of fractured vertebra on T1-weighted images (≤59.52%), C7–S1 sagittal vertical axis (≥3.25 cm), and intravertebral cleft. Internal validation showed a corrected area under the curve of 0.794. A cutoff of ≤1 point was chosen to classify a low risk of SFCV, for which only 6 of 100 patients (6%) had SFCV. A cutoff of ≥4 points was chosen to classify a high risk of SFCV, for which 28 of 41 (68.3%) had SFCV.

Conclusion

The SFCV score was found to be a simple preoperative method for identification of patients at low and high risk of postoperative SFCV. This model could be applied to individual patients and aid in the decision-making before percutaneous kyphoplasty.
New estimates of the storage permanence and ocean co-benefits of enhanced rock weathering
Authors: Kanzaki Yoshiki , Planavsky Noah J , Reinhard Christopher T
Published: April 2023

Avoiding many of the most severe consequences of anthropogenic climate change in the coming century will very likely require the development of “negative emissions technologies”—practices that lead to net carbon dioxide removal (CDR) from Earth's atmosphere. However, feedbacks within the carbon cycle place intrinsic limits on the long-term impact of CDR on atmospheric CO2 that are likely to vary across CDR technologies in ways that are poorly constrained. Here, we use an ensemble of Earth system models to provide new insights into the efficiency of CDR through enhanced rock weathering (ERW) by explicitly quantifying long-term storage of carbon in the ocean during ERW relative to an equivalent modulated emissions scenario. We find that although the backflux of CO2 to the atmosphere in the face of CDR is in all cases significant and time-varying, even for direct removal and underground storage, the leakage of initially captured carbon associated with ERW is well below that currently assumed. In addition, net alkalinity addition to the surface ocean from ERW leads to significant increases in seawater carbonate mineral saturation state relative to an equivalent emissions trajectory, a co-benefit for calcifying marine organisms. These results suggest that potential carbon leakage from the oceans during ERW is a small component of the overall ERW life cycle and that it can be rigorously quantified and incorporated into technoeconomic assessments of ERW at scale.
Cocaine-induced granulomatosis with polyangiitis—an under-recognized condition
Authors: Gill Charn , Sturman Joseph , Ozbek Leyla , Henderson Scott R , Burns Aine , Hamour Sally , Pepper Ruth J , McClelland Lisha , Chanouzas Dimitrios , Gane Simon , Salama Alan D , Harper Lorraine
Published: April 2023

Objectives

Cocaine and cocaine mixed with levamisole are increasingly used in the UK and result in significant direct nasal damage in addition to promoting vasculitis. Our aims were as follows: (1) to identify the main symptoms and presentation of cocaine-induced vasculitis; (2) to provide evidence regarding the best practice for the investigation and diagnosis of cocaine-induced vasculitis; and (3) to analyse the clinical outcomes of patients in order to understand the optimal management for the condition.

Methods

We performed a retrospective case series analysis of patients presenting with cocaine-induced midline destructive lesions or vasculitis compatible with granulomatosis with polyangiitis (GPA) from two large tertiary vasculitis clinics between 2016 and 2021.

Results

Forty-two patients (29 Birmingham, 13 London) with cocaine-induced midline lesions or systemic disease were identified. The median age was 41 years (range 23–66 years). Current cocaine use was common, and 20 of 23 samples provided were positive when routine urine toxicology was performed; 9 patients who denied ever using cocaine were identified as using cocaine based on urine toxicology analysis, and 11 who stated they were ex-users still tested positive. There was a high incidence of septal perforation (75%) and oronasal fistula (15%). Systemic manifestations were less common (27%), and only one patient had acute kidney injury. Fifty-six per cent of our patients were PR3-ANCA positive, with none testing positive for MPO-ANCA. Symptom remission required cocaine discontinuation even when immunosuppression was administered.

Conclusion

Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy. The ANCA pattern is not specific for cocaine-induced midline destructive lesions. Treatment should be focused on cocaine cessation and conservative management in the first instance in the absence of organ-threatening disease.
The effects of receiving diet roughage inclusion on performance, health, and serum metabolite characteristics of newly received beef calves
Authors: Robison Colton A , Pierce Kaitlyn N , Reuter Ryan R , Warner Andrea L , Wilson Blake K
Published: April 2023

Current dogma suggests increased dietary roughage may improve calf health at the expense of performance during receiving. In experiment 1, the effects of increasing dietary roughage on performance and clinical health of high-risk heifers was evaluated over a 56-d receiving period. Heifers (n = 589; initial body weight; BW = 230 ± 33 kg) were sourced from Oklahoma livestock auctions from April through October of 2019. Heifers were randomly assigned to pens, which were randomly assigned to 1 of 3 experimental dietary treatments in a randomized complete block design. Diets contained either: 1) 15% roughage (R15), 2) 30% roughage (R30), or 3) 45% roughage (R45) in the form of prairie hay. Orthogonal contrasts were used to test for linear and quadratic responses among experimental treatments. There was a linear decrease in overall average daily gain (ADG; P ≤ 0.0001) with increasing roughage inclusion which resulted in a linear decrease (P ≤ 0.0001) in heifer final BW. A linear increase (P ≤ 0.01) was observed for overall dry matter intake (DMI), and overall gain:feed (G:F) decreased linearly (P ≤ 0.0001) as dietary roughage concentration increased. A quadratic response to decreasing roughage was observed (P = 0.02) for the percent of calves treated three times for bovine respiratory disease (BRD). No other responses (P ≥ 0.11) were detected in animal health variables. In experiment 2, Angus steers (n = 12) and heifers (n = 6; BW = 272 ± 28 kg) were acquired from a single ranch in Oklahoma to evaluate the same experimental dietary treatments on serum metabolite concentrations. Animals were randomly assigned to experimental treatments, with animal serving as the experimental unit in experiment 2. Statistical models for serum metabolites in experiment 2 were analyzed using repeated measures with the effects of treatment, time, and treatment × time. In experiment 2, there were tendencies for treatment × time interactions for blood urea nitrogen (BUN; P = 0.07) and nonesterified fatty acid (NEFA; P = 0.06) concentrations. No metabolites were affected by treatment (P ≥ 0.11), while all metabolites were impacted by time (P ≤ 0.02). In summary, growth performance was improved in calves as dietary roughage concentration decreased with minimal impacts on health and serum metabolites. These results suggest that diets containing as little as 15% roughage can be used during receiving to improve calf performance without compromising calf health when fibrous byproducts are included in the diet.
Sucrose promotes branch-thorn occurrence of Lycium ruthenicum through dual effects of energy and signal
Authors: Li Lujia , Qiao Yang , Qi Xinyu , Liu Wen , Xu Weiman , Dong Shurui , Wu Yiming , Cui Jianguo , Wang Yucheng , Wang Qin-Mei
Published: April 2023

Lycium ruthenicum is an important ecoeconomic thorny shrub. In this study, the L. ruthenicum plants of a clone showed two types of ‘fewer leaves without thorn’ and ‘more leaves with thorns’ under the same condition after transplanting. Microscopic observation revealed that the apical buds of the thornless (Thless) and thorny (Thorny) branches should be selected as materials for further study. RNA-Seq analysis showed that the KEGG pathway of starch and sucrose metabolism and differentially expressed genes of sugar transport protein 13 (SUT13), sucrose synthase (SUS), trehalose-phosphate phosphatase (TPP) and trehalose-phosphate synthase (TPS) were significantly up-regulated in Thorny. The results of qRT-PCR confirmed the accuracy and credibility of the RNA-Seq. The content of sucrose in Thorny was significantly higher than that in Thless, but the content of trehalose-6-phosphate (T6P) was opposite. Leaf-clipping treatments reduced sucrose content and inhibited the occurrence/development of branch-thorns; exogenous sucrose of 16 g l−1 significantly promoted the occurrence and growth of branch-thorns, and the promotion effects were significantly higher than those treated with non-metabolizable sucrose analogs (isomaltolose and melitose). These findings suggested that sucrose might play a dual role of energy and signal in the occurrence of branch-thorns. Higher sucrose supply in apical buds from more leaves promoted the occurrence of branch-thorns via a lower content of T6P and higher expression levels of SUS, TPP and TPS, whereas fewer leaves inhibited the occurrence. The molecular hypothesis model of the leaf number/sucrose supply regulating the occurrence of branch-thorns in L. ruthenicum was established in the study, which provides foundation for breeding both Thless L. ruthenicum and Thless types of other species.
Comparative functional analysis of PdeNAC2 and AtVND6 in the tracheary element formation
Authors: Kim Min-Ha , Cho Jin-Seong , Tran Thi Ngoc Anh , Nguyen Thi Thu Tram , Park Eung-Jun , Im Jong-Hee , Han Kyung-Hwan , Lee Hyoshin , Ko Jae-Heung
Published: April 2023

Tracheary elements (i.e. vessel elements and tracheids) are highly specialized, non-living cells present in the water-conducting xylem tissue. In angiosperms, proteins in the VASCULAR-RELATED NAC-DOMAIN (VND) subgroup of the NAC (NAM, ATAF1,2, and CUC2) transcription factor family (e.g. AtVND6) are required for the differentiation of vessel elements through transcriptional regulation of genes responsible for secondary cell wall formation and programmed cell death. Gymnosperms, however, produce only tracheids, the mechanism of which remains elusive. Here, we report functional characteristics of PdeNAC2, a VND homolog in Pinus densiflora, as a key regulator of tracheid formation. Interestingly, our molecular genetic analyses show that PdeNAC2 can induce the formation of vessel element-like cells in angiosperm plants, demonstrated by transgenic overexpression of either native or NAC domain-swapped synthetic genes of PdeNAC2 and AtVND6 in both Arabidopsis and hybrid poplar. Subsequently, genome-wide identification of direct target (DT) genes of PdeNAC2 and AtVND6 revealed 138 and 174 genes as putative DTs, respectively, but only 17 genes were identified as common DTs. Further analyses have found that PdeNAC2 does not control some AtVND6-dependent vessel differentiation genes in angiosperm plants, such as AtVRLK1, LBD15/30 and pit-forming Rho-like GTPases from plant (ROP) signaling genes. Collectively, our results suggest that different target gene repertoires of PdeNAC2 and AtVND6 may contribute to the evolution of tracheary elements.
Functional Outcomes of Primary Arthrodesis (PA) Versus Open Reduction and Internal Fixation (ORIF) in the Treatment of Lisfranc Injuries
Authors: Aneja Arun , Gal Zsombor T. , Dawson Ashley N. , Sneed Chandler R. , Kalbac Tyler , Pectol Richard W. , Kavolus Matthew W. , Griffin Jarod T. , Leonard Elizabeth H. , Foster Jeffrey A. , Kinchelow Daria L. , Srinath Arjun
Published: April 2023

Objectives:

To determine whether primary arthrodesis (PA) or open reduction and internal fixation (ORIF) results in better functional outcomes through patient-reported outcome measures (PROMs). Reoperation rates and surgical characteristics among the 2 groups are evaluated as well.

Design:

A retrospective cohort study.

Setting:

Level 1 trauma center.

Patients:

Eighty-one patients treated using PA or ORIF for Lisfranc injuries between January 2010 and January 2019.

Main Outcome Measurements:

PROMs were collected using the validated Foot and Ankle Ability Measure questionnaire. Follow-up ranged from 1 to 10 years posttreatment.

Results:

Two hundred patients underwent ORIF, and 72 patients underwent PA. Eighty-one of 272 patients responded to the questionnaire. The Foot and Ankle Ability Measure revealed activities of daily living subscores for PA and ORIF of 69.78 ± 18.61 and 73.53 ± 25.60, respectively (P = 0.48). The Sports subscores for PA (45.81 ± 24.65) and ORIF (56.54 ± 31.13) were not significantly different (P = 0.11). Perceived levels of activities of daily living (P = 0.32) and Sports (P = 0.81) function, compared with preinjury levels, were also not significantly different between the 2 groups. Rates of reoperation were nearly identical for PA (28.1%) and ORIF (30.6%) (P = 1.00).

Conclusion:

Our results suggest that neither PA nor ORIF is superior regarding functional outcomes or rates of reoperation in the surgical treatment of Lisfranc injuries when appropriately triaged by the treating surgeon.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Does PGT-A affect cumulative live birth rate?
Authors: Seckin Serin , Forman Eric J.
Published: April 2023

Purpose of review

Preimplantation genetic testing for the purpose of aneuploidy screening (PGT-A) has increased in use over the last decade.

Recent findings

Whether PGT-A benefits all of the patients that choose to employ it has been a concern, as recent studies have highlighted a potential decrease in cumulative live birth rate (CLBR) for younger patients undergoing embryo transfer. However, there are limitations to many of these studies and the intended benefit of PGT-A, which is to aid as a selection tool, thus increasing the live birth rate per transfer, must not be ignored.

PGT-A was never intended to increase CLBR. The purpose of PGT-A is to maximize the chance at live birth per transfer while minimizing the risk of clinical miscarriage, ongoing aneuploid pregnancy and futile transfers. However, if it harms CLBR in the process that has to be taken into consideration. This review will discuss PGT-A in terms of its benefits, risks, and how it has been shown to affect the cumulative live birth rate within in-vitro fertilization cycles.
Antagonizing apolipoprotein J chaperone promotes proteasomal degradation of mTOR and relieves hepatic lipid deposition
Authors: Duan Shuangdi , Qin Nong , Pi Jiayi , Sun Pei , Gao Yating , Liu Lamei , Li Zenghui , Li Ya , Shi Liyang , Gao Qiang , Qiu Ye , Tang Songqing , Wang Chun-Hsiang , Chen Tzu-Ying , Wang Sin-Tian , Young Kung-Chia , Sun Hung-Yu
Published: April 2023

Background and Aims:

Overnutrition-induced activation of mammalian target of rapamycin (mTOR) dysregulates intracellular lipid metabolism and contributes to hepatic lipid deposition. Apolipoprotein J (ApoJ) is a molecular chaperone and participates in pathogen-induced and nutrient-induced lipid accumulation. This study investigates the mechanism of ApoJ-regulated ubiquitin-proteasomal degradation of mTOR, and a proof-of-concept ApoJ antagonist peptide is proposed to relieve hepatic steatosis.

Approach and Results:

By using omics approaches, upregulation of ApoJ was found in high-fat medium-fed hepatocytes and livers of patients with NAFLD. Hepatic ApoJ level associated with the levels of mTOR and protein markers of autophagy and correlated positively with lipid contents in the liver of mice. Functionally, nonsecreted intracellular ApoJ bound to mTOR kinase domain and prevented mTOR ubiquitination by interfering FBW7 ubiquitin ligase interaction through its R324 residue. In vitro and in vivo gain-of-function or loss-of-function analysis further demonstrated that targeting ApoJ promotes proteasomal degradation of mTOR, restores lipophagy and lysosomal activity, thus prevents hepatic lipid deposition. Moreover, an antagonist peptide with a dissociation constant (Kd) of 2.54 µM interacted with stress-induced ApoJ and improved hepatic pathology, serum lipid and glucose homeostasis, and insulin sensitivity in mice with NAFLD or type II diabetes mellitus.

Conclusions:

ApoJ antagonist peptide might be a potential therapeutic against lipid-associated metabolic disorders through restoring mTOR and FBW7 interaction and facilitating ubiquitin-proteasomal degradation of mTOR.
The future of hepatology
Authors: Friedman Scott L. , Sanyal Arun J.
Published: April 2023

The field of hepatology has made impressive progress over its ~75 years of existence. Advances in understanding liver function and its dysregulation in disease, genetic determinants of disease, antiviral therapy, and transplantation have transformed the lives of patients. However, there are still significant challenges that require ongoing creativity and discipline, particularly with the emergence of fatty liver diseases, as well as managing autoimmune disease, cancer, and liver disease in children. Diagnostic advances are urgently needed to accelerate risk stratification and efficient testing of new agents with greater precision in enriched populations. Integrated, holistic care models should be extended beyond liver cancer to diseases like NAFLD with systemic manifestations or extrahepatic comorbidities such as cardiovascular disease, diabetes, addiction, and depressive disorders. To meet the growing burden of asymptomatic liver disease, the workforce will need to be expanded by incorporating more advanced practice providers and educating other specialists. The training of future hepatologists will benefit from incorporating emerging skills in data management, artificial intelligence, and precision medicine. Continued investment in basic and translational science is crucial for further progress. The challenges ahead are significant, but with collective effort, the field of hepatology will continue to make progress and overcome obstacles.
Obstacles to implement machine perfusion technology in routine clinical practice of transplantation: Why are we not there yet?
Authors: Flores Carvalho Mauricio , Boteon Yuri L. , Guarrera James V. , Modi Pranjal R. , Lladó Laura , Lurje Georg , Kasahara Mureo , Dutkowski Philipp , Schlegel Andrea
Published: April 2023

Machine perfusion of solid human organs is an old technique, and the basic principles were presented as early as 1855 by Claude Barnard. More than 50 years ago, the first perfusion system was used in clinical kidney transplantation. Despite the well-known benefits of dynamic organ preservation and significant medical and technical development in the last decades, perfusion devices are still not in routine use. This article describes the various challenges to implement this technology in practice, critically analyzing the role of all involved stakeholders, including clinicians, hospitals, regulatory, and industry, on the background of regional differences worldwide. The clinical need for this technology is discussed first, followed by the current status of research and the impact of costs and regulations. Considering the need for strong collaborations between clinical users, regulatory bodies, and industry, integrated road maps and pathways required to achieve a wider implementation are presented. The role of research development, clear regulatory pathways, and the need for more flexible reimbursement schemes is discussed together with potential solutions to address the most relevant hurdles. This article paints an overall picture of the current liver perfusion landscape and highlights the role of clinical, regulatory, and financial stakeholders worldwide.
Long-term Use of Proton Pump Inhibitors is Associated With An Increased Risk of Nonalcoholic Fatty Liver Disease
Authors: Huang Hangkai , Liu Zhening , Guo Yanjun , Zeng Yan , Shen Shuxia , Xu Chengfu
Published: April 2023

Backgrounds:

The adverse effects of long-term use of proton pump inhibitors (PPIs) have led to growing concern. The association between PPIs use and the risks of nonalcoholic fatty liver disease (NAFLD) remains controversial.

Goal:

The aim of this study was to investigate the association between PPIs use and the risks of NAFLD among the general adult population in the United States.

Study:

We performed a cross-sectional study by extracting data from the National Health and Nutrition Examination Survey of 2017 to 2018. The association between PPIs use and NAFLD risks was analyzed by weighted multivariate logistic regression.

Results:

Among the 4238 participants included in this study, 2167 were diagnosed with NAFLD. In the multivariate logistic regression model, PPIs use was associated with increased risks of NAFLD [odds ratio (OR): 1.318, 95% CI: 1.044-1.663; P=0.020]. This association was nonsignificant in participants taking PPIs for ˂5 years (OR: 0.846, 95% CI: 0.579-1.238; P=0.390), whereas it remained significant in participants taking PPIs for more than 5 years (OR: 2.016, 95% CI: 1.366-2.975; P=0.031). Further analysis showed that the use of PPIs was positively associated with risks of severe hepatic steatosis (OR: 1.451, 95% CI: 1.034-2.036; P=0.031) but not with mild-to-moderate steatosis (OR: 1.242, 95% CI: 0.886-1.741; P=0.208).

Conclusions:

This study indicated that taking PPIs was associated with increased risks of NAFLD, especially severe hepatic steatosis. Awareness should be raised regarding the potential risks of NAFLD when prescribing PPIs.
Comparison of Decellularized Human Dermal Scaffolds versus Bovine Collagen/Elastin Matrices for in vivo Engineering of Axially Vascularized Soft Tissue Flaps in Rats
Authors: Falkner Florian , Mayer Simon A , Heuer Miriam , Brune Jan , Helt Hannah , Bigdeli Amir K , Dimmler Arno , Heimel Patrick , Thiele Wilko , Sleeman Jonathan , Bergmeister Helga , Schneider Karl H , Kneser Ulrich , Thomas Benjamin
Published: April 2023

Introduction:

Free flap-based soft tissue reconstruction comes at the price of donor-site morbidity. Providing an opportunity to overcome this issue, the arteriovenous loop (AVL) technique allows for the de novo generation of axially vascularized soft tissue flaps from vein grafts embedded into different matrices. Thus far, the application of the AVL technique has been limited by insufficient long-term volume retention and poor tissue stability. Therefore, we investigated the suitability of a novel human dermal scaffold to improve volume retention and tissue stability.

Methods:

AVLs were created in 28 immunocompetent rats and embedded in either decellularized human dermal scaffolds (experimental group, n=14, Epiflex) or bovine collagen/elastin matrices (control group, n=14, MatriDerm) in subcutaneous polytetrafluoroethylene chambers. The weight and volume of engineered tissues, as well as the extent of angiogenesis and proportion of proliferating cells were compared between both groups on postoperative days (POD) 21 and 28 via immunohistochemistry and micro-computed tomography (μCT).

Results

On POD 28, both groups displayed homogeneous microvascular networks upon histopathology and µCT. Mean microvessel counts and surface areas as well as the percentage of proliferating cells did not differ between both groups. However, the experimental human scaffold group displayed significantly smaller volume loss and significantly less extent of tissue degradation compared to bovine matrix controls (volume retention: 102±5% vs. 27±7% on POD 21, 79±12% vs. 12±7% on POD 28; p<0.0001, respectively).

Conclusions

Compared to bovine matrices, decellularized human scaffolds allow for superior volume retention and tissue stability of de novo engineered soft tissue AVL flaps in rats.
APPLICATION OF A MICROSUCTION BACKGROUND DEVICE FOR MICROANASTAMOSIS IN A RAT FEMORAL VESSEL MODEL
Authors: Khajuria Ankur , Jeong Hyung Hwa , Papavasiliou Theodora , Chatzimichail Stelios , Hong Joon Pio
Published: April 2023

Performing microvascular anastomoses can be challenging when oedematous fluids and blood continuously flood/compromise the field of view. Intermittent irrigation and suctioning disturb workflow, requires an assistant, and can increase risk of arterial thrombosis, from vessels being drawn into suction drains. We developed and patented a novel, 3D-printed background device with microfluidic capabilities, to provide autonomous, continuous irrigation and suction to optimise operator autonomy and efficiency. We then tested this in a rat femoral vessel model. Twelve end-to-end anastomoses were performed by 2 senior microsurgeons (6 conventional, 6 suction-assisted background, SAB) in a rat femoral artery model. The primary outcome was time taken to complete the anastomosis. Secondary outcomes included: the validated Structured assessment of microsurgery skills (SAMS) score; and the total number of ‘wiping’ events to obtain field clarity. Each procedure was recorded, and videos were independently rated by two blinded experts using the SAMS score. Time taken to complete the anastomosis was greater in the conventional group compared to SAB group (741.7 secs + 203.1 vs 584 secs + 155.9, p=0.007). The median SAMS score was lower in the conventional group compared with SAB group (32.3 + 1.4 versus 38.3 + 1.5, p=0.001). The median number of ‘wiping’ events was significantly greater in the conventional group compared with the SAB group (13 + 2.2 versus 1.7 + 1.2, p<0.001). We showed that a novel, microfluidic background device allows continuous, irrigation and suctioning, without need for assistant, and optimises the efficiency of the microvascular anastomosis.
Reconstruction of type IIIB thumb hypoplasia using a vascularized hemi-metatarsal composite tissue flap
Authors: Fang Xia , Yu Aiping , Dai Xinyi , Bai Huikai , Zhou Jiateng , Li Dongdong , Du Xingchao , Tian Jingshun , Zhou Shengbo , Wang Bin
Published: April 2023

Purpose:

The aim of this study is to report the clinical outcomes of vascularized hemi-metatarsal composite tissue transfer for the reconstruction of type IIIB hypoplastic thumbs.

Methods:

Twenty-eight patients with type IIIB hypoplastic thumbs treated with vascularized hemi-metatarsal composite tissue transfer were included in this retrospective study with a mean follow-up of 2.4 years. Preoperative digital subtraction angiography (DSA) was performed to examine the vessel variance. Clinical measures included the grip and pinch strength, scar status and Kapandji thumb opposition score. Subjective Pediatric outcomes data collection instrument (PODCI) scores and parent satisfaction were also evaluated.

Results:

Radial arteries were hypoplastic in 82.1% of the cases and the common palmar digital artery was chosen as the recipient vessel for the tissue transfer. There was no neurovascular complication. The only donor site complication was a metatarsal fracture which healed with casting. Key pinch and tripod pinch were 29.5% and 45.8% of the normal side respectively. The mean grip strength was 51.7% of the unaffected side. The mean Kapandji score was 6. The PODCI scores were high for global function, upper extremity function, transfer and basic mobility, happiness, and comfort. The Vancouver Scar Scale showed an average score of 2.1. All parents were satisfied with the clinical outcomes.

Conclusions:

Vascularized hemi-metatarsal composite tissue transfer for type IIIB thumb hypoplasia can provide improved subjective outcomes and is a feasible method for the attainment of a 5-digit hand.
Identifying Contributing Factors Associated With Dental Adverse Events Through a Pragmatic Electronic Health Record–Based Root Cause Analysis
Authors: Kalenderian Elsbeth , Bangar Suhasini , Yansane Alfa , Tran Duong , Sedlock Emily , Xiao Yan , Urata Janelle , Olson Greg , Franklin Amy , Kookal Krishna , Ibarra-Noriega Ana , Tungare Sayali , Tokede Oluwabunmi , Spallek Heiko , White Joel M. , Walji Muhammad F.
Published: April 2023

Objective

This study assessed contributing factors associated with dental adverse events (AEs).

Methods

Seven electronic health record–based triggers were deployed identifying potential AEs at 2 dental institutions. From 4106 flagged charts, 2 reviewers examined 439 charts selected randomly to identify and classify AEs using our dental AE type and severity classification systems. Based on information captured in the electronic health record, we analyzed harmful AEs to assess potential contributing factors; harmful AEs were defined as those that resulted in temporary moderate to severe harm, required hospitalization, or resulted in permanent moderate to severe harm. We classified potential contributing factors according to (1) who was involved (person), (2) what were they doing (tasks), (3) what tools/technologies were they using (tools/technologies), (4) where did the event take place (environment), (5) what organizational conditions contributed to the event? (organization), (6) patient (including parents), and (7) professional-professional collaboration. A blinded panel of dental experts conducted a second review to confirm the presence of an AE.

Results

Fifty-nine cases had 1 or more harmful AEs. Pain occurred most frequently (27.1%), followed by nerve injury (16.9%), hard tissue injury (15.2%), and soft tissue injury (15.2%). Forty percent of the cases were classified as “temporary not moderate to severe harm.” Person (training, supervision, and fatigue) was the most common contributing factor (31.5%), followed by patient (noncompliance, unsafe practices at home, low health literacy, 17.1%), and professional-professional collaboration (15.3%).

Conclusions

Pain was the most common harmful AE identified. Person, patient, and professional-professional collaboration were the most frequently assessed factors associated with harmful AEs.
Associations of functional human leucocyte antigen class I groups with HIV viral load in a heterogeneous cohort
Authors: Zucco Adrian G. , Bennedbæk Marc , Ekenberg Christina , Gabrielaite Migle , Leung Preston , Polizzotto Mark N. , Kan Virginia , Murray Daniel D. , Lundgren Jens D. , MacPherson Cameron R.
Published: April 2023

Objective:

Human leucocyte antigen (HLA) class I alleles are the main host genetic factors involved in controlling HIV-1 viral load (VL). Nevertheless, HLA diversity has proven a significant challenge in association studies. We assessed how accounting for binding affinities of HLA class I alleles to HIV-1 peptides facilitate association testing of HLA with HIV-1 VL in a heterogeneous cohort.

Design:

Cohort from the Strategic Timing of AntiRetroviral Treatment (START) study.

Methods:

We imputed HLA class I alleles from host genetic data (2546 HIV+ participants) and sampled immunopeptidomes from 2079 host-paired viral genomes (targeted amplicon sequencing). We predicted HLA class I binding affinities to HIV-1 and unspecific peptides, grouping alleles into functional clusters through consensus clustering. These functional HLA class I clusters were used to test associations with HIV VL.

Results:

We identified four clades totaling 30 HLA alleles accounting for 11.4% variability in VL. We highlight HLA-B∗57:01 and B∗57:03 as functionally similar but yet overrepresented in distinct ethnic groups, showing when combined a protective association with HIV+ VL (log, β −0.25; adj. P-value < 0.05). We further demonstrate only a slight power reduction when using unspecific immunopeptidomes, facilitating the use of the inferred functional HLA groups in other studies

Conclusion:

The outlined computational approach provides a robust and efficient way to incorporate HLA function and peptide diversity, aiding clinical association studies in heterogeneous cohorts. To facilitate access to the proposed methods and results we provide an interactive application for exploring data.
A novel, evidence-based, comprehensive clinical decision support system improves outcomes for patients with traumatic rib fractures
Authors: Jones Emma K. , Ninkovic Ivana , Bahr Matthew , Dodge Sarah , Doering Michael , Martin David , Ottosen Julie , Allen Tadashi , Melton Genevieve B. , Tignanelli Christopher J.
Published: April 2023

BACKGROUND

Traumatic rib fractures are associated with high morbidity and mortality. Clinical decision support systems (CDSS) have been shown to improve adherence to evidence-based (EB) practice and improve clinical outcomes. The objective of this study was to investigate if a rib fracture CDSS reduced hospital length of stay (LOS), 90-day and 1-year mortality, unplanned ICU transfer, and the need for mechanical ventilation. The independent association of two process measures, an admission EB order set and a pain-inspiratory-cough score early warning system, with LOS were investigated.

METHODS

The CDSS was scaled across nine US trauma centers. Following multiple imputation, multivariable regression models were fit to evaluate the association of the CDSS on primary and secondary outcomes. As a sensitivity analysis, propensity score matching was also performed to confirm regression findings.

RESULTS

Overall, 3,279 patients met inclusion criteria. Rates of EB practices increased following implementation. On risk-adjusted analysis, in-hospital LOS preintervention versus postintervention was unchanged (incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 0.97–1.15, p = 0.2) but unplanned transfer to the ICU was reduced (odds ratio, 0.28; 95% CI, 0.09–0.84, p = 0.024), as was 1-year mortality (hazard ratio, 0.6; 95% CI, 0.4–0.89, p = 0.01). Provider utilization of the admission order bundle was 45.3%. Utilization was associated with significantly reduced LOS (IRR, 0.87; 95% CI, 0.77–0.98; p = 0.019). The early warning system triggered on 34.4% of patients; however, was not associated with a significant reduction in hospital LOS (IRR, 0.76; 95% CI, 0.55–1.06; p = 0.1).

CONCLUSION

A novel, user-centered, comprehensive CDSS improves adherence to EB practice and is associated with a significant reduction in unplanned ICU admissions and possibly mortality, but not hospital LOS.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Funding the war in America: A look in the mirror
Authors: Hynes Allyson M. , Weaver Jessica L. , Hatchimonji Justin S. , Sperry Jason L. , Sanchez Sabrina E. , Seamon Mark J. , Kheirbek Tareq , Scantling Dane R.
Published: April 2023

BACKGROUND

Health care political action committees (HPACs) historically contribute more to candidates opposing firearm restrictions (FRs), clashing with their affiliated medical societies. These societies have increasingly emphasized the prevention of firearm violence and it is not known if recent contributions by their HPACs have aligned with their stated goals. We hypothesized that such HPACs still contribute similar amounts toward legislators up for reelection opposing FR.

METHODS

We identified HPACs of medical societies endorsing one or both calls-to-action against firearm violence published in the Annals of Internal Medicine (2015, 2019). House of Representatives (HOR) votes on H.R.8, a background checks bill, were characterized from GovTrack. We compiled HPAC contributions between the H.R.8 vote and election to HOR members up for re-election from the National Institute on Money in Politics. Our primary outcome was total campaign contributions by H.R.8 stance. Secondary outcomes included percentage of politicians funded and total contributions.

RESULTS

Nineteen societies endorsed one or both call-to-action articles. Three hundred eighty-five of 430 HOR members ran for reelection in 2020. Those endorsing H.R.8 (n = 226, 59%) received $2.8 M for $4,750 (interquartile range [IQR], $1000–$15,500) per candidate. Those opposing (n = 159, 41%) received $1.5 M for $2,500 (IQR, $0–$11,000) per candidate (p = 0.0057). Health care political action committees donated toward a median of 20% (IQR, 7–28) of candidates endorsing H.R.8 and 9% (IQR, 4–22) of candidates opposing H.R.8 (p = 0.0014). Those endorsing H.R.8 received 1,585 total contributions for a median of 3 (IQR, 1–10) contributions per candidate, while those opposing received 834 total contributions for a median of 2 (IQR, 0–7) contributions per candidate (p = 0.0029).

CONCLUSION

Politicians voting against background checks received substantial contributions toward reelection from the HPACs of societies advocating for firearm restrictions. However, this is the first study to suggest that HPAC's contributions have become more congruent with their respective societies. Further alignment of medical society goals and their HPAC political contributions could have a profound impact on firearm violence.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Effect of passive and active ventilation on malaria mosquito house entry and human comfort: an experimental study in rural Gambia
Authors: Carrasco-Tenezaca Majo , Jawara Musa , Lee Daniel Sang-Hoon , Holmes Matthew S. , Ceesay Sainey , McCall Phillip , Pinder Margaret , D'Alessandro Umberto , Knudsen Jakob B. , Lindsay Steve W. , Wilson Anne L.
Published: April 2023

Rural houses in sub-Saharan Africa are typically hot and allow malaria mosquitoes inside. We assessed whether passive or active ventilation can reduce house entry of malaria mosquitoes and cool a bedroom at night in rural Gambia. Two identical experimental houses were used: one ventilated and one unventilated (control). We evaluated the impact of (i) passive ventilation (solar chimney) and (ii) active ventilation (ceiling fan) on the number of mosquitoes collected indoors and environmental parameters (temperature, humidity, CO
2
, evaporation). Although the solar chimney did not reduce entry of
Anopheles gambiae
sensu lato
, the ceiling fan reduced house entry by 91% compared with the control house. There were no differences in indoor nightly temperature, humidity or CO
2
between intervention and control houses in either experiment. The solar chimney did not improve human comfort assessed using psychrometric analysis. While the ceiling fan improved human comfort pre-midnight, in the morning it was too cool compared with the control house, although this could be remedied through provision of blankets. Further improvements to the design of the solar chimney are needed. High air velocity in the ceiling fan house probably reduced mosquito house entry by preventing mosquito flight. Improved ventilation in houses may reduce malaria transmission.
The mechanisms of siRNA selection by plant Argonaute proteins triggering DNA methylation
Authors: Liu Wei , Shoji Keisuke , Naganuma Masahiro , Tomari Yukihide , Iwakawa Hiro-oki
Published: April 2023

The model plantArabidopsis thalianaencodes as many as ten Argonaute proteins (AGO1–10) with different functions. Each AGO selectively loads a set of small RNAs by recognizing their length and 5′ nucleotide identity to properly regulate target genes. Previous studies showed that AGO4 and AGO6, key factors in DNA methylation, incorporate 24-nt small-interfering RNAs with 5′ adenine (24A siRNAs). However, it has been unclear how these AGOs specifically load 24A siRNAs. Here, we biochemically investigated the siRNA preference of AGO4, AGO6 and their chimeric mutants. We found that AGO4 and AGO6 use distinct mechanisms to preferentially load 24A siRNAs. Moreover, we showed that the 5′ A specificity of AGO4 and AGO6 is not determined by the previously known nucleotide specificity loop in the MID domain but rather by the coordination of the MID and PIWI domains. These findings advance our mechanistic understanding of how small RNAs are accurately sorted into different AGO proteins in plants.
Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC
Authors: Liu Songlei , Li Li , Zhang Fan , van Sambeek Björn , Appleton Evan , Ng Alex H. M. , Khoshakhlagh Parastoo , Chen Yuting , Garcia-Corral Mariana , Wu Chun-Ting , Huang Jeremy Y. , Tan Yuqi , Chao George , Aach John , Tam Jenny , Lim Elaine T. , Raychaudhuri Soumya , Church George M.
Published: April 2023

The ability to differentiate stem cells into human cell types is essential to define basic mechanisms and therapeutics, especially for cell types not routinely accessible by biopsies. But while engineered expression of transcription factors (TFs) identified through TF screens has been found to rapidly and efficiently produce some cell types, generation of other cell types that require complex combinations of TFs has been elusive. Here we develop an iterative, pooled single-cell TF screening method that improves the identification of effective TF combinations using the generation of human microglia-like cells as a testbed: Two iterations identified a combination of SPI1, CEBPA, FLI1, MEF2C, CEBPB, and IRF8 as sufficient to differentiate human iPSC into microglia-like cells in 4 days. Characterization of TF-induced microglia demonstrated molecular and functional similarity to primary microglia. We explore the use of single-cell atlas reference datasets to confirm identified TFs and how combining single-cell TF perturbation and gene expression data can enable the construction of causal gene regulatory networks. We describe what will be needed to fashion these methods into a generalized integrated pipeline, further ideas for enhancement, and possible applications.
Fusarium culmorumproduces NX-2 toxin simultaneously with deoxynivalenol and 3-acetyl-deoxynivalenol or nivalenol (submitted to Toxins)
Authors: Schiwek Simon , Alhussein Mohammad , Rodemann Charlotte , Budragchaa Tuvshinjargal , Beule Lukas , Tiedemann Andreas von , Karlovsky Petr
Published: April 2023

Fusarium culmorumis a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotox-ins of the trichothecene B group. These toxins are also produced byF. graminearumspecies complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates ofF. graminearumfrom North America. Only these isolates and a few strains of a yet to be characterizedFusariumspecies from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20F. culmorumstrains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). InF. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded byTRI1that is unable to oxidize C-8. InF. culmorum, producers and non-producers of NX-2 possess identicalTRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature ofF. culmorum.

Key result

Isolates ofFusarium culmorumobtained from different hosts at different locations over several dec-ades produced NX-2, which is a type A trichothecene structurally related to 3-ADON.
From silence to song: Testosterone triggers extensive transcriptional changes in the female canary HVC
Authors: Ko Meng-Ching , Frankl-Vilches Carolina , Bakker Antje , Sohnius-Wilhelmi Nina , Alcami Pepe , Gahr Manfred
Published: April 2023

Seasonal song production in canaries, influenced by gonadal hormones, is a well-documented phenomenon. We explored testosterone-induced song development in adult female canaries—a behavior rarely exhibited naturally. Gene regulatory networks in the song-controlling brain area HVC were compared at multiple time points (1 hour to 14 days) post-treatment with those of placebo-treated controls, paralleling HVC and song development. Females began vocalizing within four days of testosterone treatment, with song complexity and HVC volume increasing progressively over two weeks. Rapid transcriptional changes involving 2,739 genes preceded song initiation. Over two weeks, 9,913 genes—approximately 64% of the canary’s protein-coding genome—were differentially expressed, with 98% being transiently regulated. These genes are linked to various biological functions, with early changes at the cellular level and later changes affecting the nervous system level after prolonged hormone exposure. Our findings suggest that testosterone-induced song development is accompanied by extensive and dynamic transcriptional changes in the HVC, implicating widespread neuronal involvement. The data reveal extensive transcriptomic changes, including alterations in steroid receptor expression and numerous transcription factors, coinciding with significant neural transformations. These changes underpin the gradual emergence of singing behavior, providing insights into the neural basis of seasonal behavioral patterns.