bluuebunny/crossref_metadata_2025 huggingface dataset:
Health insurance rights and access to health care for trans people: The social construction of medical necessity
Authors: Kirkland Anna , Talesh Shauhin , Perone Angela K.
Published: December 2021

Health care rights for transgender and/or nonbinary people have dramatically expanded in recent years, including in insurance coverage for the treatments and procedures they need. Yet, trans people themselves still identify health insurance problems as a top priority for research and policy change because of significant difficulties gaining and using coverage. Wrangling over coverage determinations happens through multiple types of interactions, bureaucratic, interpersonal, and medical. When these interactions become difficult, it is because key terms such as medical necessity are both powerful and indeterminate. This study examines how trans people and health care intermediaries navigate the health insurance process and contest the meaning of medical necessity in coverage determinations. These disputes constitute the ground-level reality for instantiating health care rights to gender affirming care. Relying on analysis of contract language and 32 interviews with people who sought gender-affirming care and allied professionals, we find that health insurance policy language, interpretation, and implementation often create disadvantages and barriers for trans people who attempt to access care. Our study highlights how the contested life of insurance policy terminology produces a reality for rights but also details the mechanisms through which insurance-mediated care is a socially contested and negotiated process
Hydrothermal alteration at the basalt‐hosted Vista Alegre impact structure, Brazil
Authors: Alsemgeest Jitse , Brouwer Fraukje M. , Auqué Luis F. , Hauser Natalia , Reimold Wolf Uwe
Published: December 2021

Hydrothermal systems provide a possible habitat for early life and are key targets in the quest for life outside Earth. In impact craters on Mars, hydrous minerals can represent products of impact‐generated hydrothermal systems (IGHS) or minerals already present in the crust and exposed during impact‐caused excavation. Because of its basaltic target rock, similar in composition to Martian crust, the Vista Alegre impact structure in Brazil is one of the very few analog structures that may reveal the origin of these minerals, if evidence of hydrothermal alteration is established. This work presents the results of a systematic search for evidence of hydrothermal alteration at the Vista Alegre impact structure. Four types of alteration were identified, all within a 2.5–3.0 km radius from the crater center: a zircon‐bearing melt veinlet, two sets of hydrothermal veins consisting predominantly of calcite and chabazite, and local alteration comprising saponite. Thermodynamic modeling suggests subsequent heating and cooling for each of the hydrothermal vein sets. Combined thermodynamic and spectrometric evidence indicates that development of a vigorous IGHS is unlikely. If similar processes occur on Mars, hydrous minerals are more likely preimpact phases exposed by excavation, rather than being formed through an IGHS.
A new rupicolous species of Puya (Bromeliaceae) with pendulous inflorescence from the Eastern Cordillera of Colombia
Authors: Aguirre‐Santoro Julián , Ordóñez‐Blanco Juan Camilo , Betancur Julio
Published: December 2021

Puya pendula, a new species from rocky outcrops at mid elevations of the Eastern Cordillera of Colombia is described here. This new species is unique within Puya because of its rupicolous habit, pendulous inflorescence, glabrescent floral bracts, pedicels and sepals covered with glandular hairs, and white petals with a green central longitudinal stripe. The description is complemented with comments on the geographical distribution of the species, habitat, conservation status and a complete taxonomic discussion of its affinities within Puya.
Could female steroids lead to osteonecrosis of the jaw?
Authors: Costa Samuel M. , Mota Viviani C. , Greco Bernardo B. , Bueno Sebastião C. , Amaral Marcio B. F.
Published: December 2021

Tibolone (TB) is a synthetic female steroid with an estrogenic hormonal profile that has been related to suppress bone resorption and neoformation. This drug usage has been increasing over the last few years, particularly among pre‐ and post‐menopause woman. This study presents the first known case of TB related osteonecrosis of the jaw and explains the relationship between the drug and the osteonecrosis pathogenesis. One hypothesis for the small number of cases relating TB and medication related osteonecrosis of the jaws is that the drug promotes a different impact on bone metabolism. In this cases it is mandatory a local trauma. On the illustrative case we present within this letter, the installation of implants was what triggered the alterations and the necrosis. All surgeons should be aware of these drugs, and all the patients in the group of menopausal conditions should be asked about the use of this medication.
Long‐term outcomes of mandibular reconstruction using non‐vascularised rib grafts following large ameloblastoma resection in Ethiopia
Authors: de Berker Henry T. , Honeyman Calum , Patel Vinod , Yonis Elyas , Eshete Mekonen , Martin Dominique , McGurk Mark
Published: December 2021

Aim

Ameloblastomas are odontogenic tumours that often require radical excision and mandibular reconstruction. This is challenging in resource‐limited settings where access to microsurgery is often scarce or absent. Currently, some patients are left without reconstruction, and others with bulky metal plates prone to complications. This leads to disfigurement and poor functional outcomes. We aim to establish robust long‐term outcomes for non‐vascularised autologous rib grafts for patients in this setting.

Materials and Methods

Twelve adult patients with large ameloblastomas underwent hemimandibulectomy and rib graft reconstruction during international surgical collaborations in Ethiopia between 2012 and 2015. A long‐term follow‐up was conducted in rural Ethiopia in February 2017.

Results

Follow‐up was possible for seven patients (58% of those treated). Mean post‐operative follow‐up time was 42.9 months (SD 11.7; range 24–60 months). Early complications were four superficial surgical site infections. Late complications were two cases of wire extrusion and one of keloid scarring. There were no graft failures. Patients reported reduced social stigma (p = 0.001) and pain (p = 0.03), excellent function and 100% satisfaction.

Conclusion

When situational factors preclude the use of microsurgery, bundle rib grafts offer a reliable alternative for total mandibular reconstruction for patients after ameloblastoma resection. Mild complications were experienced by most patients, but these were straightforward to manage and the rib grafts still took well, being surprisingly resistant to infection. Importantly, this technique is associated with long‐term improvements in social stigma and quality of life for patients.
Long‐Term Clinical Outcomes and Survivorship of Total Hip Arthroplasty for Pyogenic Arthritis: A Retrospective Cohort Study of 168 Hips
Authors: Zeng Wei‐Nan , Zeng Lin , Guo Qiang , Yu Qiu‐Ping , Wang Hao‐Yang , Luo Ze‐Yu , Pei Fu‐Xing , Zhou Zong‐Ke
Published: December 2021

Objective

The aim of the present study was to evaluate the 10‐year outcomes of cementless total hip arthroplasty (THA) in adult patients with the late sequelae of septic arthritis of the hip.

Methods

We followed 166 consecutive patients (168 hips) who underwent cementless THA between March 2001 and December 2011. There were 79 men and 87 women, with a mean age of 50.4 years (range 21–76 years) at the time of index THA, all of whom had hip osteoarthritis secondary to hip pyogenic infection. The average duration of follow up was 10.6 years (range 6.9–17.2 years). Preoperative and postoperative clinical ratings were evaluated, including the hip dysfunction and osteoarthritis outcome score (HOOS), the Harris hip score (HHS), range of motion, a 100‐point visual analog scale for hip pain, and the severity of limp and limb length discrepancy (LLD). The anteroposterior and lateral radiographs of the hip and full‐length view of the lower extremities were obtained to assess the position of the components, radiolucent lines, osteolysis, loosening of components, and heterotopic ossification. The intraoperative and postoperative complications were also recorded.

Results

The mean HSS and hip pain score were 44.2 points (range 29–66 points) and 42.5 points (range 32–64 points), respectively, before the index surgery and significantly improved to 88.1 points (range 78–96 points) and 15.1 points (range 10–26 points), respectively, at final follow‐up examination. The HOOS and range of motion also improved significantly. The mean limb length discrepancy was reduced from 2.6 to 0.8 cm. The limp at last follow‐up examination was moderate in 3 cases because of hip osteoarthritis in the other limb, slight in 26, and absent in 137. A radiolucent line was observed in 12 hips (7.1%) around the acetabular or femoral components. A progressive radiolucent line around the undersized femoral stem in all zones was seen in 1 hip, resulting in aseptic loosening and breakage of the femoral component. There were 8 cases of intraoperative fracture, 7 cases of dislocation, and 7 cases of transient nerve palsy. Recurrence of infection occurred in 2 hips. Revision surgery was conducted in 2 hips because of isolated loosening of the acetabular cup and the femoral stem, respectively. Kaplan–Meier survival was 97% at 10 years, with revision for any reason with any component as an end‐point.

Conclusion

Improved surgical techniques and development of components with various sizes provided favorable results for cementless THA conducted for late sequelae of sepsis in these young and active patients. Although the incidence of complications was relatively high, the complications were treated successfully.
Knee Scores of Patients with Non‐Lateral Compartmental Knee Osteoarthritis Undergoing Mobile, Fixed‐Bearing Unicompartmental Knee and Total Knee Arthroplasties: A Randomized Controlled Trial
Authors: Wu Li‐ping , Mayr Hermann O , Zhang Xing , Huang Yuan‐qiao , Chen Yuan‐zhuang , Li Yu‐ming
Published: December 2021

Objective

To evaluate knee scores and clinical efficacies of patients with non‐lateral unicompartmental knee osteoarthritis (OA) who randomly underwent mobile‐bearing (MB) unicompartmental knee arthroplasty (UKA), fixed‐bearing (FB) UKA, and total knee arthroplasty (TKA).

Methods

From September 2015 to February 2017, a prospective, randomized, parallel, single‐center trial of 180 patients (78 males and 102 females; 63.3 ± 6.9 years) with non‐lateral compartmental knee OA was performed in the first author‐affiliated hospital. The patients were randomly divided into three groups (each group included 60 patients) and received medial cemented Oxford phase 3 MB UKA, medial cemented Link FB UKA, or cemented DePuy Sigma PFC TKA, respectively. A similar perioperative management and fast‐track surgery program was carried out for all patients. The knee scores at 3‐year follow‐up after operation and clinical efficacies of these three groups of patients were recorded, investigated, and compared.

Results

Primarily, compared to the TKA group, the UKA groups (MB UKA and FB UKA) had shorter operative time (median 63.2 < 67.1 min), less bleeding (8.6 < 30.0 mL), earlier resumption of walking without crutches (3.0 < 8.0 days) and walking up and down the stairs (5.0 < 10.0 days) (P < 0.001), higher FJS scores (78.0 > 74.5) (P = 0.007), better results in all knee scores (except VAS and KSS function scores) (P < 0.05), and a larger maximum flexion angle of the knee at the 3‐year follow‐up (123.0° > 96.0°) (P = 0.001). Secondarily, compared to the TKA group, the MB UKA group showed better results in the Western Ontario and McMaster Universities index (WOMAC) stiffness (83.6 > 79.6), WOMAC total (86.3 > 83.2), Oxford knee score (OKS) (20.0 < 23.0), Forgotten Joint Score (FJS) (78.5 > 74.5), and a larger maximum flexion angle of the knee (123.0 > 96.0) (P < 0.05). Moreover, the FB UKA group showed higher Hospital for Special Surgery Knee Score (HSS) (91.0 > 88.5), WOMAC stiffness (84.3 > 79.6), WOMAC function (85.2 > 81.7), WOMAC total scores (87.6 > 83.2), and a larger maximum flexion angle of the knee (119.0° > 96.0°) than the TKA group (P < 0.05). Overall, there was no significant difference in all knee scores and maximum flexion angles of the knee for the MB UKA and FB UKA groups (P > 0.05). There was one case with original bearing dislocation in MB UKA group. One patient with displacement of the femoral component caused by a fall injury, and another patient, who lost his life in a car accident, were involved in the FB UKA group. There was an infection case and an intermuscular vein thrombosis case in TKA group.

Conclusion

UKA showed more advantages than TKA; however, there was no significant difference between the MB UKA and FB UKA groups for treatment of non‐lateral compartmental knee OA.
Stover return and nitrogen application affect soil organic carbon and nitrogen in a double‐season maize field
Authors: Liu Y. X. , Pan Y. Q. , Yang L. , Ahmad S. , Zhou X. B.
Published: December 2021

Cultivation techniques have an important influence on grain yield of maize. This experiment investigated the effect of stover return (SR) and different nitrogen (N) application rate on soil organic carbon (SOC) composition, soil nutrient and maize yield.

Different nitrogen application rate 100 (N100), 150 (N150), 200 (N200), 250 (N250) or 300 (N300) kg ha−1 applied to the maize field with stover return and without stover return traditional planting (TP) method.

Nitrogen application rate and stover return affected the SOC, labile organic carbon (LOC), microbial biomass (MBC), NO3−‐N, NH4+‐N and maize yield. Soil N, soil carbon content and maize yield of SR were all higher than TP. The SOC content of SR and TP were 9.67 and 9.19 g kg−1, respectively. Nitrogen application was significantly and positively correlated with soil MBC, LOC, SOC, NO3−‐N, NH4+‐N and yield. The maximum values of SOC composition, soil nutrients and maize yield were reached at SR with 250 kg ha−1.

Stover return with application of N 250 kg ha−1 significantly increased the growth attribute and maize yield in subtropical region compared with traditional planting.
Recent developments in male fertility evaluation, sperm cryopreservation and artificial fertilisation, and their potential application to decapod crustacean aquaculture
Authors: Aquino Jon Irish Legaspi , Elliott Lisa , Zeng Chaoshu , Paris Damien B.B.P.
Published: December 2021

To maximise productivity, a better understanding of the underlying causes of subfertility that lead to inferior offspring and high mortality is imperative. In decapod crustaceans, most research has focused on female reproductive performance, with little attention given to male fertility. Paternal genetic contribution is critical to both successful embryonic and post‐embryonic development. Assessment of sperm quality can be a direct method to determine male subfertility in decapods. Sperm quality parameters such as sperm concentration and morphology have traditionally been used to determine male reproductive performance, but these procedures are time‐consuming and can only assess a limited number of sperm cells and males. Alternative diagnostic biomarkers used widely in humans and other mammals could be adapted to decapod crustaceans and may be more indicative of sperm fertilisation competence and male reproductive performance. These predictive biomarkers use fluorescent cellular dyes and high‐throughput flow cytometry or computer‐assisted sperm microscopic analysis to evaluate sperm viability, mitochondrial function, acrosome reaction and DNA fragmentation. This review examines current and advanced biomarkers to evaluate sperm quality and further explores state‐of‐the‐art procedures of sperm cryopreservation (conventional vs. vitrification techniques) and artificial fertilisation in decapod crustaceans. Sperm freezing coupled with artificial fertilisation in decapods permits the long‐term storage, controlled timing and selection of individuals for reproduction. Collectively, these tools can be applied to commercial broodstock management to improve productivity and accelerate selective breeding in the crustacean aquaculture industry.
Investigating the well‐being implications of mobile money access and usage from a multidimensional perspective
Authors: Sakyi‐Nyarko Carlos , Ahmad Ahmad Hassan , Green Christopher J.
Published: December 2021

Using household survey data gleaned from Ghana, we carried out a microeconometric analysis of the relationship between mobile money (m‐money) and multidimensional well‐being. A key feature of this paper is the computation of a well‐being index, incorporating important household welfare dimensions including health, education, and wealth, thus allowing an examination of the link between m‐money and well‐being from a multidimensional perspective. Using instrumental variable probit models with phone ownership and public sector employment as instruments, we find that although access to m‐money is important it is its usage that has a profound well‐being effect. We also explore alternative specifications of the models in which access to, and usage of, m‐money explains the variations in the individual well‐being components, which also relate to the Sustainable Development Goals. The results from these alternative specifications suggest that there are significant welfare disparities between those who just have access to m‐money and those who use it frequently. The policy implication of this finding is that measures that encourage m‐money usage would not only promote financial inclusion but also lead to improvement in welfare outcomes and living standards, especially in rural households.
Sibling caring roles and responsibilities when a child suffers from a chronic illness
Authors: Hilário Ana Patrícia
Published: December 2021

Siblings' lives and well‐being are potentially affected in profound ways when their brother or sister suffers from a chronic illness in childhood. The shift in the care of chronically ill children from the hospital to the home in recent years has had an impact on family relationships and interactions. Whilst studies on caregiving have focused on the parental care of children who are chronically ill; siblings may nevertheless take on some caring roles and responsibilities. This article intends to make a novel contribution to the sociological literature on siblings, caring, and chronic illness by presenting a review of the literature addressing siblings' caring roles and responsibilities in families of children with a chronic illness. Knowing about the caring roles and responsibilities undertaken by siblings when a brother or sister has a chronic illness, may be beneficial to healthcare professionals and influence their caring practice. In addition, this work may contribute to a better understanding of family relationships and further improve healthcare policies.
A prospective interventional study to assess the impact of a ‘structured compact training’ on knowledge and skills of safe blood transfusion practices among nurses working in a tertiary care institute
Authors: Malhotra Sheetal , Negi Gita , Sharma Suresh Kumar , Kaur Ravneet
Published: December 2021

Introduction

There is scarce information on the baseline knowledge and practices of nursing officers in relation to administration of blood components. We set out to evaluate the influence of training on their knowledge and skills through Kirkpatrick's levels of Training Evaluation.

Materials and Methods

This interventional cross sectional study of 7 months duration conducted in a tertiary care teaching institute involved 200 nursing officers. Hundred were assigned to study/intervention group and 100 were assigned to control/ comparison group by systematic random sampling. Knowledge was tested in different domains—blood components, pre‐transfusion checks, transfusion process, post‐transfusion process and blood administration practice.

Results

The baseline knowledge scores of intervention and control group were similar—15.16 ± 4.11 and 15.02 ± 4.75 (p = 0.831). Post‐intervention (phase I) after 1 month, the scores improved significantly for domain A, B, C, D and E to 4.3 ± 2.21 (p = 0.0001), 3.46 ± 2.15 (p = 0.0001), 7.02 ± 3.55 (p = 0.0001), 2.51 ± 1.46 (p = 0.0012), and 5.86 ± 3.61 (p = 0.0018) respectively. In phase II, after 3 months of training, and the scores were significantly better from baseline for all domains except E. For domain A, B, C, D and E, scores were 3.82 ± 2.46 (p = 0.0001), 3.53 ± 1.98 (p = 0.0001), 7.38 ± 3.87 (p = 0.0001), 2.48 ± 1.55 (p = 0.0035), and 5.86 ± 3.61 (p = 0.95) respectively.

Conclusions

Our study showed that baseline scores were low in the nursing officers. No significant difference was found in baseline scores in subject and control population. However, post‐intervention, a significant improvement in scores was observed in the study group across all domains.
Neurogenic keratoconjunctivitis sicca in 34 dogs: A case series
Authors: Galley Amy P. , Beltran Elsa , Tetas Pont Roser
Published: December 2021

Objective

To describe the clinical findings, imaging features, underlying conditions, treatment, and progression of dogs presented between 2010 and 2019 with neurogenic keratoconjunctivitis sicca (NKCS).

Methods

Dogs diagnosed with NKCS were searched in the clinical database. Inclusion criteria were STT‐1 readings <15 mm/min, clinical signs of KCS with concurrent ipsilateral xeromycteria.

Results

Thirty‐four cases were identified. Mean age at presentation was 8.2 years, median 8.9 years (0.3–14.7). Twenty dogs were male, and 14 dogs were female. Concurrent neurological deficits included facial neuropathy (n = 13, 38%), peripheral vestibular syndrome (n = 10, 29%), and Horner's syndrome (n = 5, 15%). Advanced imaging was acquired in 53% of cases (n = 18). Etiologies included idiopathic (n = 18, 53%), endocrinopathy (n = 6, 18%), otitis interna (n = 4, 12%), head trauma (n = 3, 9%), iatrogenic (post‐TECA‐LBO, n = 1, 3%), brainstem mass (n = 1, 3%), and an area of inflammation in the pterygopalatine fossa (n = 1, 3%). Treatment for NKCS was initiated in most cases (n = 30, 88%) including: oral pilocarpine 2% and lacrimostimulant (n = 19), oral pilocarpine 2% only (n = 3), or lacrimostimulant only (n = 8). A mean time follow‐up of 3.7 months, median 3 months (1–14) was available in 23 cases (68%). Eleven cases with follow‐up were responsive (48%) with resolution of the clinical signs in a median time 4 months (1–10), and all of them were treated with oral pilocarpine (±lacrimostimulant).

Conclusions

Most cases presented as idiopathic NKCS; in others, an underlying cause of facial neuropathy was identified. All responsive cases were treated with oral pilocarpine 2%.
Sensitivity Analysis of the Levelized Cost of Electricity for a Particle-Based Concentrating Solar Power System
Authors: González-Portillo Luis F. , Albrecht Kevin J. , Sment Jeremy , Mills Brantley , Ho Clifford K.
Published: December 2021

This study presents a sensitivity analysis of the levelized cost of electricity (LCOE) for a particle-based system with the costs of the most current components. New models for the primary heat exchanger, thermal energy storage, and tower are presented and used to establish lower and upper bounds for these three components. The rest of component costs such as particle cost, cavity cost, and lift cost are set to lower and upper bounds estimating an uncertainty between 25% and 50%. Other relevant parameters related to lift and storage performance are also included in the analysis with the same uncertainty. This study also includes an upgrade to the receiver model by including the wind effect in the efficiency, which was not included in previous publications and may have a big impact in the system design. A parametric analysis shows the optimum values of solar multiple, storage hours, tower height, and concentration ratio, and a probabilistic analysis provides a cumulative distribution function for a range of LCOE values. The results show that the LCOE could be below $0.06/kWh with a probability of between 80% and 90%, where the costs of primary heat exchanger, particles, and lifts have largest contribution to the variance of the LCOE.
Correlating Time-Resolved Pressure Measurements With Rim Sealing Effectiveness for Real-Time Turbine Health Monitoring
Authors: DeShong Eric T. , Peters Benjamin , Berdanier Reid A. , Thole Karen A. , Paynabar Kamran , Gebraeel Nagi
Published: December 2021

Purge flow is bled from the upstream compressor and supplied to the under-platform region to prevent hot main gas path ingress that damages vulnerable under-platform hardware components. A majority of turbine rim seal research has sought to identify methods of improving sealing technologies and understanding the physical mechanisms that drive ingress. While these studies directly support the design and analysis of advanced rim seal geometries and purge flow systems, the studies are limited in their applicability to real-time monitoring required for condition-based operation and maintenance. As operational hours increase for in-service engines, this lack of rim seal performance feedback results in progressive degradation of sealing effectiveness, thereby leading to reduced hardware life. To address this need for rim seal performance monitoring, this study utilizes measurements from a one-stage turbine research facility operating with true-scale engine hardware at engine-relevant conditions. Time-resolved pressure measurements collected from the rim seal region are regressed with sealing effectiveness through the use of common machine learning techniques to provide real-time feedback of sealing effectiveness. Two modeling approaches are presented that use a single sensor to predict sealing effectiveness accurately over a range of two turbine operating conditions. Results show that an initial purely data-driven model can be further improved using domain knowledge of relevant turbine operations, which yields sealing effectiveness predictions within 3% of measured values.
Nonequilibrium Thermal Fluctuations of Flow in Thermal Systems
Authors: Li Wei
Published: December 2021

Fouling is detrimental to the heat transfer performance of concentrated solar power plant components where heat exchange takes place with the cooling tower water. Wave elements cause an expression of deep insight of the fouling formation. A new physical concept of wave element is proposed; it is the wave interface between two molecule groups with an infinitesimal temperature difference in fluid. It is generated by density difference, which results from temperature difference. Tiny temperature differences always exist everywhere in a fluid. When a fluid is in motion, wave elements are generated among molecule groups. Wave motion and Brownian motion can serve as the two basic forms of motion of the molecules in flow. Temperature controls Brownian motion. Temperature differences and the fluid's motion cause the wave elements. Nonequilibrium thermal fluctuations present as wave elements in a flow. A wave element appears as wave behavior along the space and time dimensions that are based on the continuity relation. The direct experimental evidence for wave elements cannot be directly established at the present scientific testing cap ability because the temperature difference of two molecule groups adjoining each other in a flow is infinitesimal. A series of “enlarged size” experiments are conducted involving the cooling tower water fouling to show the wave elements’ behaviors by tracing the molecules’ movement. The experimental study presents that the wave interface along the space and time dimensions simultaneously exists between two densities due to fluid motion. The experimental evidence and theoretical analysis support each other.
Dr. Richard C. Nelson: Respected as the Father of the Japanese Society of Biomechanics
Authors: Miyashita Mitsumasa
Published: December 2021

The reasons for the renaming of the Japanese Society of Kinesiology to the Japanese Society of Biomechanics are explained, and the importance of the International Congress of Biomechanics, the International Society of Biomechanics, and Richard Nelson are outlined.
Interleukin-13-Overexpressing Mice Represent an Advanced Preclinical Model for Detecting the Distribution of Antimycobacterial Drugs within Centrally Necrotizing Granulomas
Authors: Walter Kerstin , Kokesch-Himmelreich Julia , Treu Axel , Waldow Franziska , Hillemann Doris , Jakobs Nikolas , Lemm Ann-Kathrin , Schwudke Dominik , Römpp Andreas , Hölscher Christoph
Published: December 2021

The
Mycobacterium tuberculosis
-harboring granuloma with a necrotic center surrounded by a fibrous capsule is the hallmark of tuberculosis (TB). For a successful treatment, antibiotics need to penetrate these complex structures to reach their bacterial targets.
Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis
Authors: Kim Ju Sang , Kim Yong-hyun , Lee Sang Haak , Kim Yee Hyung , Kim Jin-woo , Kang Ji Young , Kim Sung Kyoung , Kim Seung Joon , Kang Yun-Seong , Kim Tae-hyung , Mok Jeongha , Byun Min Kwang , Park Hye Jung , Joh Joon-sung , Park Yong Bum , Lim Hyeong-Seok , Choi Hongjo , Lee Seung Heon , Kim Hyejin , Yang Jeongseong , Kim Hyunji , Shen Xianlin , Alsultan Abdullah , Cho InSook , Geiter Lawrence , Shim Tae Sun
Published: December 2021

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has
in vitro
activity against Gram-positive bacteria, including
Mycobacterium tuberculosis
.
Effects of Increasing Concentrations of Rifampicin on Different Mycobacterium tuberculosis Lineages in a Whole-Blood Bactericidal Activity Assay
Authors: Verma Rupangi , Gurumurthy Meera , Yeo Benjamin Chaik Meng , Lu Qingshu , Naftalin Claire M. , Paton Nicholas I.
Published: December 2021

High-dose rifampicin improved bactericidal activity and culture conversion in early-phase trials, done mainly in Africa. We performed a whole-blood bactericidal activity (WBA) study to determine whether the effects of high-dose rifampicin differ across globally relevant strains and whether effects are similar in dormant bacilli that will be required for enhancing cure.
Combination of Pharmacokinetic and Pathogen Susceptibility Information To Optimize Meropenem Treatment of Gram-Negative Infections in Critically Ill Patients
Authors: Liebchen Uwe , Weinelt Ferdinand , Scharf Christina , Schroeder Ines , Paal Michael , Zoller Michael , Kloft Charlotte , Jung Jette , Michelet Robin
Published: December 2021

Meropenem is one of the most frequently used antibiotics to treat life-threatening infections in critically ill patients. This study aimed to develop a meropenem dosing algorithm for the treatment of Gram-negative infections based on intensive care unit (ICU)-specific resistance data. Antimicrobial susceptibility testing of Gram-negative bacteria obtained from critically ill patients was carried out from 2016 to 2020 at a tertiary care hospital.
Prevalence of Antifungal Resistance, Genetic Basis of Acquired Azole and Echinocandin Resistance, and Genotyping of Candida krusei Recovered from an International Collection
Authors: Khalifa Hazim O. , Hubka Vit , Watanabe Akira , Nagi Minoru , Miyazaki Yoshitsugu , Yaguchi Takashi , Kamei Katsuhiko
Published: December 2021

This study was designed to evaluate the prevalence of antifungal resistance, genetic mechanisms associated with
in vitro
induction of azole and echinocandin resistance and genotyping of
Candida krusei
, which is intrinsically resistant to fluconazole and is recovered from clinical and nonclinical sources from different countries. Our results indicated that all the isolates were susceptible or had the wild phenotype (WT) to azoles, amphotericin B, and only 1.27% showed non-WT for flucytosine.
Identifying Targets of Protective Antibodies against Severe Malaria in Papua, Indonesia, Using Locally Expressed Domains of Plasmodium falciparum Erythrocyte Membrane Protein 1
Authors: Rambhatla Janavi S. , Tonkin-Hill Gerry Q. , Takashima Eizo , Tsuboi Takafumi , Noviyanti Rintis , Trianty Leily , Sebayang Boni F. , Lampah Daniel A. , Marfurt Jutta , Price Ric N. , Anstey Nicholas M. , Papenfuss Anthony T. , Damelang Timon , Chung Amy W. , Duffy Michael F. , Rogerson Stephen J.
Published: December 2021

Severe
Plasmodium falciparum
malaria kills many African children, and lack of antibody immunity predisposes to severe disease. A critical antibody target is the
P. falciparum
erythrocyte membrane 1 (PfEMP1) family of multidomain proteins, which are expressed on the infected erythrocyte surface and mediate parasite sequestration in deep organs.
Mcc1229, an Stx2a-Amplifying Microcin, Is Produced
In Vivo
and Requires CirA for Activity
Authors: Nawrocki Erin M. , Hutchins Laura E. , Eaton Kathryn A. , Dudley Edward G.
Published: December 2021

Enterohemorrhagic
Escherichia coli
(EHEC) strains, including the foodborne pathogen
E. coli
O157:H7, are responsible for thousands of hospitalizations each year. Various environmental triggers can modulate pathogenicity in EHEC by inducing the expression of Shiga toxin (Stx), which is encoded on a lambdoid prophage and transcribed together with phage late genes.
Genetic Suppression Meets Structure Prediction: Probing a Spore Germination Receptor Complex
Authors: Moir Anne , Popham David L.
Published: December 2021

Despite the thousands of spore germinant receptor operons identified in genomes of Bacilli and Clostridia, understanding how the three essential receptor components act as a signal transduction machine in germination remains limited. The paper by Amon et al. in this issue uses the classical genetic approach of suppression to define a region of likely interaction between the GerAA and GerAB proteins: it provides a first glimpse into potential events within the receptor complex.
Supplemental Material: Mississippian southern Laurentia tuffs came from a northern Gondwana arc
Authors: Tian Hepeng , al. et
Published: December 2021

Description of tuffs, analytical methods, and results, Figures S1–S7, and Tables S1–S5.
The Properties of Thermochemical Remanent Magnetization Acquired by Slow Laboratory Cooling of Titanomagnetite-Bearing Basalt Samples from Different Temperatures and the Results of the Thellier Method
Authors: Gribov S. K. , Shcherbakov V. P. , Tsel’movich V. A. , Aphinogenova N. A.
Published: December 2021

Abstract—The experiments have been carried out on the acquisition of thermochemical remanent magnetization (TCRM) in basalt samples containing titanomagnetite (TM) with the Curie temperature Тс ~200°C by their rapid heating to maximum temperatures Т* from 450 to 530°C followed by slow cooling in the laboratory magnetic field Blab. At different stages of the preliminary thermal treatment of the initial samples, a set of magnetomineralogical studies including electron microscopy, X-ray diffraction and thermomagnetic analyzes, and measurements of magnetic hysteresis parameters were performed. It is shown that as early as the very beginning of the cooling process, all samples demonstrate explosive growth of TCRM corresponding to the stage of rapid single-phase oxidation of the initial titanomagnetite fraction of basalt, and that TCRM is acquired by the increase of Тс and volume of single-phase oxidized parts of TM grains as well as by the growth of the volume of Ti-depleted (relative to the initial TM) cells of microstructure of the subsequent oxidative exsolution. The Arai–Nagata diagrams for the samples carrying TCRM have a form of a broken line consisting of two linear segments. The low-temperature interval T < Т* corresponds to a mixture of thermochemical and thermoremanent (TRM) magnetizations and gives a slightly overestimated Blab because of the effect of a low cooling rate during the acquisition of TCRM and TRM. The high-temperature interval corresponds to pure TCRM and the Blab strength determined from this interval is underestimated by 20–27%. It is recommended to reject samples whose Araii–Nagata diagram has two or more linear segments against the background single-component NRM.
Nanocracks upon Fracture of Oligoclase
Authors: Vettegren V. I. , Ponomarev A. V. , Mamalimov R. I. , Shcherbakov I. P.
Published: December 2021

Abstract—The spectrum of fractoluminescence (FL) upon fracture of the surface of oligoclase is obtained. The analysis of the spectrum has shown that fracture of crystals leads to the formation of electronically excited free radicals ≡Si−O• and Fe3• ions as well as electron traps. FL consisted of a set of the signals with the intensities varying by an order of magnitude. The duration of the signals was ~50 ns and the time interval between them varied from ~0.1 to 1 μs. Each signal contained four maxima associated with the destruction of barriers preventing the motion of dislocations along the sliding planes. These breakthroughs cause the formation of the smallest (“primary”) cracks. All other, larger cracks are formed by the coalescence of the “primary” cracks. The sizes of “primary” cracks range from ~10 to 20 nm and the time of their formation is 16 ns. The distribution of cracks by size (surface areas of crack walls) is power law with the exponent –1.9.
Reducing carbon footprint of inhalers: analysis of climate and clinical implications of different scenarios in five European countries
Authors: Pernigotti Daniele , Stonham Carol , Panigone Sara , Sandri Federica , Ferri Rossella , Unal Yasemin , Roche Nicolas
Published: December 2021

Background

Inhaled therapies are key components of asthma and chronic obstructive pulmonary disease (COPD) treatments. Although the use of pressurised metered-dose inhalers (pMDIs) accounts for <0.1% of global greenhouse gas emissions, their contribution to global warming has been debated and efforts are underway to reduce the carbon footprint of pMDIs. Our aim was to establish the extent to which different scenarios led to reductions in greenhouse gas emissions associated with inhaler use, and their clinical implications.

Methods

We conducted a series of scenario analyses using asthma and COPD inhaler usage data from 2019 to model carbon dioxide equivalent (CO2e) emissions reductions over a 10-year period (2020–2030) in the UK, Italy, France, Germany and Spain: switching propellant-driven pMDIs for propellant-free dry-powder inhalers (DPIs)/soft mist inhalers (SMIs); transitioning to low global warming potential (GWP) propellant (hydrofluoroalkane (HFA)-152a) pMDIs; reducing short-acting β2-agonist (SABA) use; and inhaler recycling.

Results

Transition to low-GWP pMDIs and forced switching to DPI/SMIs (excluding SABA inhalers) would reduce annual CO2e emissions by 68%–84% and 64%–71%, respectively, but with different clinical implications. Emission reductions would be greatest (82%–89%) with transition of both maintenance and SABA inhalers to low-GWP propellant. Only minimising SABA inhaler use would reduce CO2e emissions by 17%–48%. Although significant greenhouse gas emission reductions would be achieved with high rates of end-of-life recycling (81%–87% of the inhalers), transition to a low-GWP propellant would still result in greater reductions.

Conclusions

While the absolute contribution of pMDIs to global warming is very small, substantial reductions in the carbon footprint of pMDIs can be achieved with transition to low-GWP propellant (HFA-152a) inhalers. This approach outperforms the substitution of pMDIs with DPI/SMIs while preserving patient access and choice, which are essential for optimising treatment and outcomes. These findings require confirmation in independent studies.
Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers
Authors: Mao Jinzhu , Wang Dongxu , Long Junyu , Yang Xu , Lin Jianzhen , Song Yiwei , Xie Fucun , Xun Ziyu , Wang Yanyu , Wang Yunchao , Li Yiran , Sun Huishan , Xue Jingnan , Song Yang , Zuo Bangyou , Zhang Junwei , Bian Jin , Zhang Ting , Yang Xiaobo , Zhang Lei , Sang Xinting , Zhao Haitao
Published: December 2021

Background

The gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers.

Methods

Patients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy.

Results

In total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance.

Conclusions

We demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.
Radiographic clearance of chronic subdural hematomas after middle meningeal artery embolization
Authors: Catapano Joshua S , Ducruet Andrew F , Srinivasan Visish M , Rumalla Kavelin , Nguyen Candice L , Rutledge Caleb , Cole Tyler S , Baranoski Jacob F , Lawton Michael T , Jadhav Ashutosh P , Albuquerque Felipe C
Published: December 2021

Background

Few reports discuss variables associated with improved outcomes after middle meningeal artery (MMA) embolization for chronic subdural hematomas (cSDHs). We analyzed radiographic evidence of cSDH clearance after MMA embolization to elucidate optimal techniques, hematoma clearance rates, and suitable length of follow-up.

Methods

Patients who underwent MMA embolization for cSDH from January 1, 2018 through December 31, 2020 were analyzed. Patient characteristics, demographics, and technical procedural details were examined. Outcomes for cSDHs analyzed included complete or near-complete resolution at 30, 90, and 180 days following embolization. A multivariable logistic regression analysis identified variables predictive of rapid clearance and resolution of hematomas at 90 days.

Results

The study cohort comprised 66 patients with 84 treated cSDHs. The mean (SD) cSDH size differed significantly at 30-day (8.8 (4.3) mm), 90-day (3.4 (3.0) mm), and 180-day (1.0 (1.7) mm) follow-up (p<0.001). More cSDHs had complete or near-complete resolution at 180 days (92%, 67/73) than at 90 (63%, 45/72) and 30 days (18%, 15/84) post-embolization (p<0.001). Only distal embolysate penetration was independently associated with rapid clearance (OR 3.9, 95% CI 1.4 to 11.1; p=0.01) and resolution of cSDHs at 90 days (OR 5.0, 95% CI 1.7 to 14.6; p=0.003).

Conclusion

Although 63% of cSDHs with MMA embolization had complete or near-complete resolution by 90 days post-procedure, 92% reached this stage by 180 days. Therefore, 90-day follow-up may be insufficient to determine the effectiveness of MMA embolization for cSDHs, particularly compared with surgical evacuation alone. Also, distal MMA penetration may be associated with more rapid hematoma clearance.
Activation of PPCI team in the octogenarian and nonagenarians population: real-world single-centre experience
Authors: Kumar Rajesh , O’Connor Cormac , Kumar Jathinder , Kerr Brain , Malik Ihtisham , Homer Ciarrai , Abbas Syed , Arnous Samer , Ullah Ihsan , Kiernan Thomas John
Published: December 2021

Objective

Advancement in healthcare provision has led to increasing octogenarian ST elevation myocardial infarction (STEMI) presentation to hospital for early revascularisation therapies. Limited literature to date exists to suggest octogenarian STEMI population; with majority of trials excluding these age group patients. Due to an ageing population, we expect increasing rates of STEMI in the octogenarian and nonagenarian population in the future. This study seeks to identify the outcomes of patients over the age of 80 presenting with STEMI and determine the factors associated with better or worse outcome.

Patients and methods

This study is a single-centre retrospective observational study involving patients’ age 80 or older presenting with STEMI between January 2014 and December 2019. Patient data were collected by chart review and analysis of the local STEMI database. Standard Bayesian statistics were employed for analysis.

Results

1301 patients presented with STEMI during this period. 159/1301 (12.2%) were 80 years or older that fulfilled STEMI criteria, 35/159 (22.1%) were medically managed. 107/124 (86.29%) had angiographic evidence of acute total or partial thrombotic occlusion, and 97/107 were treated with primary percutaneous coronary intervention (PPCI). The activation ECG most commonly exhibited an anterior STEMI, while inferior STEMI ECGs had the strongest positive predictive value. PPCI group had a 30-day mortality rate of 20% (p=0.07) and 1-year mortality was 22.4%. Highest mortality was observed with cardiogenic shock, low ejection fraction, higher high sensitivity cardiac troponin T and creatinine at presentation. Conservatively managed patients had significant higher mortality rate (48% vs 22.4%, p=0.005) at 1 year.

Conclusion

Patients over the age of 80 who present with STEMI and undergo PPCI have a significantly lower mortality rate at 1 year. These patients have a 77.6% survival at 1 year, with 92.4% likelihood of discharge to home (without need for long-term nursing home care). Cardiogenic shock in this group was associated with a 1-year mortality of 87.5%. Despite the advanced age, we suggest favourable outcomes described in the absence of patients presenting with cardiogenic shock.