bluuebunny/crossref_metadata_2025 huggingface dataset:
The implication of long non-coding RNA expression profile in rheumatoid arthritis: Correlation with treatment response to tumor necrosis factor inhibitor
Authors: Wang Qiubo , Huang Xuan , Shao Yang , Liu Qingyang , Shen Jin , Xia Jinjun , Zhang Zhiqian , Wang Chunxin
Published: February 2022

Objective

This study aimed to investigate the linkage of long non-coding RNA (lncRNA) expression profile with etanercept response in rheumatoid arthritis (RA) patients.

Methods

Peripheral blood mononuclear cell (PBMC) samples were collected from 80 RA patients prior to etanercept treatment. Samples from eight responders and eight non-responders at week 24 (W24) were proposed to RNA-sequencing, then 10 candidate lncRNAs were sorted and their PBMC expressions were validated by reverse transcription quantitative chain reaction (RT-qPCR) in 80 RA patients. Subsequently, clinical response by lncRNA (CRLnc) prediction model was established.

Results

RNA-sequencing identified 254 up-regulated and 265 down-regulated lncRNAs in W24 responders compared with non-responders, which were enriched in immune or joint related pathways such as B-cell receptor signaling, osteoclast differentiation and T-cell receptor signaling pathways, etc. By reverse transcription quantitative chain reaction (RT-qPCR) validation: Two lncRNAs were correlated with W4 response, three lncRNAs were correlated with W12 response, seven lncRNAs were correlated with W24 response. Subsequently, to construct and validate CRLnc prediction model, 80 RA patients were randomly divided into test set (n = 40) and validation set (n = 40). In the test set, lncRNA RP3-466P17.2 (OR = 9.743, P = .028), RP11-20D14.6 (OR = 10.935, P = .007), RP11-844P9.2 (OR = 0.075, P = .022), and TAS2R64P (OR = 0.044, P = .016) independently related to W24 etanercept response; then CRLnc prediction model integrating these four lncRNAs presented a good value in predicting W24 etanercept response (Area Under Curve (AUC): 0.956, 95%CI: 0.896–1.000). However, in the validation set, the CRLnc prediction model only exhibited a certain value in predicting W24 etanercept response (AUC: 0.753, 95%CI: 0.536–0.969).

Conclusions

CRLnc prediction model is potentially a useful tool to instruct etanercept treatment in RA patients.
Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan
Authors: Atsumi Tatsuya , Asakura Eri , Doi Michio , Sawant Ruta , Kawaguchi Isao , Sasaki Nobuhito , Liew Danny
Published: February 2022

Objective

This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib, and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR).

Methods

Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR) 20/50/70 at 12 and 24 weeks.

Results

Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15 mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4 mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5 mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes.

Conclusions

Upadacitinib 15 mg was associated with the lowest NNT and CPR among the three Janus kinase inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD.
Material research from the viewpoint of functional motifs
Authors: Jiang Xiao-Ming , Deng Shuiquan , Whangbo Myung-Hwan , Guo Guo-Cong
Published: February 2022

As early as 2001, the need for the ‘functional motif theory’ was pointed out, to assist the rational design of functional materials. The properties of materials are determined by their functional motifs and how they are arranged in the materials. Uncovering functional motifs and their arrangements is crucial in understanding the properties of materials and rationally designing new materials of desired properties. The functional motifs of materials are the critical microstructural units (e.g. constituent components and building blocks) that play a decisive role in generating certain material functions, and can not be replaced with other structural units without the loss, or significant suppression, of relevant functions. The role of functional motifs and their arrangement in materials, with representative examples, is presented. The microscopic structures of these examples can be classified into six types on a length scale smaller than ∼10 nm with maximum subatomic resolution, i.e. crystal, magnetic, aperiodic, defect, local and electronic structures. Functional motif analysis can be employed in the function-oriented design of materials, as elucidated by taking infrared non-linear optical materials as an example. Machine learning is more efficient in predicting material properties and screening materials with high efficiency than high-throughput experimentation and high-throughput calculations. In order to extract functional motifs and find their quantitative relationships, the development of sufficiently reliable databases for material structures and properties is imperative.
Computed Tomography Texture Analysis for Predicting Clinical Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors
Authors: Park Hyo Jung , Qin Lei , Bakouny Ziad , Krajewski Katherine M , Van Allen Eliezer M , Choueiri Toni K , Shinagare Atul B
Published: February 2022

Background

The treatment responses of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) vary, requiring reliable prognostic biomarkers. We assessed the prognostic ability of computed tomography (CT) texture analysis in patients with mRCC treated with programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors.

Materials and Methods

Sixty-eight patients with mRCC treated with PD-1/PD-L1 inhibitors between 2012 and 2019 were revaluated. Using baseline and first follow-up CT, baseline and follow-up texture models were developed to predict overall survival (OS) and progression-free survival (PFS) using least absolute shrinkage and selection operator Cox-proportional hazards analysis. Patients were divided into high-risk or low-risk group, and the survival difference was assessed using Kaplan-Meier and log-rank test. Multivariable Cox models were constructed by including only the clinical variables (clinical models) and by combining the clinical variables and the texture models (combined clinical-texture models), and their predictive performance was evaluated using Harrell’s C-index.

Results

The baseline texture models distinguished longer- and shorter-term survivors for both OS (median, 60.1 vs. 17.0 months; P = .048) and PFS (5.2 vs. 2.8 months; P = .003). The follow-up texture models distinguished longer- and shorter-term overall survivors (40.3 vs. 15.2 months; P = .008) but not for PFS (5.0 vs. 3.6 months; P = .25). The combined clinical-texture model outperformed the clinical model in both predicting the OS (C-index, 0.70 vs. 0.63; P = .03) and PFS (C-index, 0.63 vs. 0.55; P = .04).

Conclusion

CT texture analysis performed at baseline and early after starting PD-1/PD-L1 inhibitors is associated with clinical outcomes of patients with mRCC.
Aureochromes maintain polyunsaturated fatty acid content in Nannochloropsis oceanica
Authors: Poliner Eric , Busch Andrea W U , Newton Linsey , Kim Young Uk , Clark Rachel , Gonzalez-Martinez Sofía C , Jeong Byeong-Ryool , Montgomery Beronda L , Farré Eva M
Published: February 2022

Nannochloropsis oceanica, like other stramenopile microalgae, is rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA). We observed that fatty acid desaturases (FADs) involved in LC-PUFA biosynthesis were among the strongest blue light-induced genes in N. oceanica CCMP1779. Blue light was also necessary for maintaining LC-PUFA levels in CCMP1779 cells, and growth under red light led to a reduction in EPA content. Aureochromes are stramenopile-specific proteins that contain a light–oxygen–voltage (LOV)-sensing domain that associates with a flavin mononucleotide and is able to sense blue light. These proteins also contain a basic leucine zipper DNA-binding motif and can act as blue light-regulated transcription factors by associating with an E-box like motif, which we found enriched in the promoters of blue light-induced genes. We demonstrated that, in vitro, two CCMP1779 aureochromes were able to absorb blue light. Moreover, the loss or reduction of the expression of any of the three aureochrome genes led to a decrease in the blue light-specific induction of several FADs in CCMP1779. EPA content was also significantly reduced in NoAUREO2 and NoAUREO4 mutants. Taken together, our results indicate that aureochromes mediate blue light-dependent regulation of LC-PUFA content in N. oceanica CCMP1779 cells.
Can biochemical traits bridge the gap between genomics and plant performance? A study in rice under drought
Authors: Melandri Giovanni , Monteverde Eliana , Riewe David , AbdElgawad Hamada , McCouch Susan R , Bouwmeester Harro
Published: February 2022

The possibility of introducing metabolic/biochemical phenotyping to complement genomics-based predictions in breeding pipelines has been considered for years. Here we examine to what extent and under what environmental conditions metabolic/biochemical traits can effectively contribute to understanding and predicting plant performance. In this study, multivariable statistical models based on flag leaf central metabolism and oxidative stress status were used to predict grain yield (GY) performance for 271 indica rice (Oryza sativa) accessions grown in the field under well-watered and reproductive stage drought conditions. The resulting models displayed significantly higher predictability than multivariable models based on genomic data for the prediction of GY under drought (Q2 = 0.54–0.56 versus 0.35) and for stress-induced GY loss (Q2 = 0.59–0.64 versus 0.03–0.06). Models based on the combined datasets showed predictabilities similar to metabolic/biochemical-based models alone. In contrast to genetic markers, models with enzyme activities and metabolite values also quantitatively integrated the effect of physiological differences such as plant height on GY. The models highlighted antioxidant enzymes of the ascorbate–glutathione cycle and a lipid oxidation stress marker as important predictors of rice GY stability under drought at the reproductive stage, and these stress-related variables were more predictive than leaf central metabolites. These findings provide evidence that metabolic/biochemical traits can integrate dynamic cellular and physiological responses to the environment and can help bridge the gap between the genome and the phenome of crops as predictors of GY performance under drought.
Pre-release Risk Assessments: Pilot Study of a Novel Tool in One Police Station in the North East of England
Authors: Lyall Alicia , Austin Helena , Alder Ross , Wild Georgina , Reid Keith , McKinnon Iain
Published: February 2022

Research in police custody risk assessment and health screening has historically been focused on detainees arrival in custody with much less emphasis on pre-release risk assessment (PRRA). This research aimed to evaluate a modified PRRA piloted in one police station in the North East of England for two weeks in March/April 2019 against College of Policing’s Authorised Professional Practice (APP) guidance. A controlled before and after study design was conducted. During the intervention phase, custody suite (A) piloted the modified PRRA whilst control custody suite (B) continued to use standard PRRA. Randomised, anonymised custody records were analysed; 300 records were taken from each suite during the intervention phase, and a further 300 from each suite during the period preceding intervention. PRRA records were scored against criteria derived from the College of Policing’s APP guidance. Improvements were seen in seven outcomes with greatest effects observed in recording risks associated with mental health, physical health and substance misuse.
Providing Opinions: State Attorneys General and State Constitutions
Authors: Cauthen James N G
Published: February 2022

Federalism scholars have increasingly recognized the impact of state attorneys general in national politics. State attorneys general also are in a unique position to contribute to the development and application of state law through their advisory opinion duties. I examine advisory opinion activity on state constitutional questions across all states for 2016–2018 in the context of legal, institutional, and political explanations developed in studies of attorney general behavior and judicial decision-making. Most opinions addressed issues of finance, legislative power or local power and were most often issued to state legislators and local officials. Republican attorneys general in Southern states with similar political cultures were most active issuing opinions, with significant party collaboration between requesters and attorneys general.
Which policy instrument do citizens and civil servants prefer? A choice experiment on Swedish marine policy
Authors: Ek Claes , Elofsson Katarina , Lagerkvist Carl-Johan
Published: February 2022

In the choice between alternative environmental policy instruments, economists tend to favor policies capable of attaining cost-efficiency, but other considerations may be more important to stakeholders. We perform a choice experiment modeled on Swedish water and marine policy to estimate preferences for different policy instruments among citizens and municipal civil servants. Both the modal citizen and the modal civil servant prefer direct regulation and subsidies to nutrient trading. Moreover, nutrient trading is unlikely to deliver sufficiently large cost savings for civil servants to prefer it to other instruments. These results are consistent with the apparent reluctance to adopt water quality trading in Europe.
UNWANTED RADIATION EXPOSURE TO RADIOSENSITIVE ORGANS DURING HAND CT
Authors: Nam Dae Jin , Moon Sun Rock , Kang Hong Je
Published: February 2022

This study aimed to investigate unwanted radiation exposure of radiosensitive organs during computed tomography (CT) scans of the hand. Furthermore, we investigated the effectiveness of a shield in reducing unwanted radiation exposure. In a prospective observational study, the patients were randomized to receive a shield during the hand CT scan. Two group of patients were further randomized to undergo multi-detector CT (MDCT) or cone-beam CT (CBCT). The radiation dose was measured in the target point and the nearest skin surface of radiosensitive organs by attached the thermoluminescent dosemeter chips. When shielding was performed, the radiation doses had decreased significantly with a mean of 79% (65–91%) in the MDCT group and 88.6% (85–93%) in the CBCT group. In the non-shielded group, the radiation doses to the radiosensitive organs decreased inversely with increasing distance, which means that the closer the target point is, the more unwanted radiation exposure increases. It is important to keep radiosensitive organs as far as possible from the target point during CT scan. In particular, it is necessary to shield the radiosensitive organs closer to the target point.

Level of Evidence: Level II, Prospective observational study.
Development of a Reference Chart for Monitoring Cancer-Related Fatigue Throughout a Supervised Exercise Program
Authors: Marker Ryan J. , Kittelson Andrew J. , Jankowski Catherine M. , Scorsone Jared J. , Peters John C. , Purcell W. Thomas
Published: February 2022

Background:

Cancer-related fatigue (CRF) is one of the most reported and functionally limiting symptoms experienced by individuals living with and beyond cancer. Exercise is effective at reducing CRF, although currently it is not possible to predict the magnitude and time course of improvement for an individual participating in an exercise program.

Objective:

To develop a reference chart of CRF improvement for individuals participating in a 3-month cancer-specific exercise program.

Methods:

In this retrospective cohort study, CRF was assessed every 2 weeks (using the FACIT-Fatigue scale, range: 0-52, with lower scores indicating greater fatigue) in 173 individuals participating in a 3-month supervised exercise program (741 observations). No cancer types were excluded and individuals were either undergoing chemotherapy and/or radiation, or within 6 months of completing treatment. The reference chart was developed using Generalized Additive Models for Location Scale and Shape.

Results:

Each participant had an average of 4 CRF observations. Lower centiles demonstrated greater improvement than higher centiles (11 points over the duration of the program for the 10th and 4 points for the 90th percentiles).

Limitations:

The population is biased to individuals self-selecting or being referred to a clinical exercise program.

Conclusions:

This reference chart provides a novel method of monitoring CRF improvement during a cancer-specific exercise program. Setting appropriate expectations and informing exercise prescription adaptation are discussed in the context of representative data from 3 participants. Future research can investigate improvements in clinical outcomes and the remote monitoring of CRF through the implementation of the reference chart.
The Impact of Sedative Choice on Intracranial and Systemic Physiology in Moderate to Severe Traumatic Brain Injury: A Scoping Review
Authors: Jeffcote Toby , Weir Timothy , Anstey James , Mcnamara Robert , Bellomo Rinaldo , Udy Andrew
Published: February 2022

Although sedative use is near-ubiquitous in the acute management of moderate to severe traumatic brain injury (m-sTBI), the evidence base for these agents is undefined. This review summarizes the evidence for analgosedative agent use in the intensive care unit management of m-sTBI. Clinical studies of sedative and analgosedative agents currently utilized in adult m-sTBI management (propofol, ketamine, benzodiazepines, opioids, and alpha-2 agonists) were identified and assessed for relevance and methodological quality. The primary outcome was the effect of the analgosedative agent on intracranial pressure (ICP). Secondary outcomes included intracranial hemodynamic and metabolic parameters, systemic hemodynamic parameters, measures of therapeutic intensity, and clinical outcomes. Of 594 articles identified, 61 met methodological review criteria, and 40 were included in the qualitative summary; of these, 33 were prospective studies, 18 were randomized controlled trials, and 8 were blinded. There was consistent evidence for the efficacy of sedative agents in the management of m-sTBI and raised ICP, but the overall quality of the evidence was poor, consisting of small studies (median sample size, 23.5) of variable methodological quality. Propofol and midazolam achieve the goals of sedation without notable differences in efficacy or safety, although high-dose propofol may disrupt cerebral autoregulation. Dexmedetomidine and propofol/ dexmedetomidine combination may cause clinically significant hypotension. Dexmedetomidine was effective to achieve a target sedation score. De novo opioid boluses were associated with increased ICP and reduced cerebral perfusion pressure. Ketamine bolus and infusions were not associated with increased ICP and may reduce the incidence of cortical spreading depolarization events. In conclusion, there is a paucity of high-quality evidence to inform the optimal use of analgosedative agents in the management of m-sTBI, inferring significant scope for further research.
Factors Affecting Rebound Phenomenon After Temporary Hemiepiphysiodesis and Implant Removal for Idiopathic Genu Valgum in Adolescent Patients
Authors: Ko Kyung Rae , Shim Jong Sup , Shin Tae Soo , Jang Min Chang
Published: February 2022

Background:

The aim of this study was to investigate factors determining postoperative courses, especially focusing on the rebound phenomenon, in adolescent patients with idiopathic genu valgum who underwent temporary hemiepiphysiodesis and implant removal.

Methods:

We identified and reviewed patients with idiopathic genu valgum treated with temporary hemiepiphysiodesis [using tension-band plates (plate group, PG) or transphyseal screws (screw group, SG)] and followed-up to skeletal maturity.

Results:

In our cohort [68 patients and their 68 limbs (randomly selected in bilateral cases)], the mean hip-knee-ankle alignment was –5.4±1.8 degrees at the time of temporary hemiepiphysiodesis (negative means valgus), 2.6±2.1 degrees at the time of implant removal, and 0.7±2.6 degrees at the last follow-up, respectively. Regarding the implants, the correction speed was not significantly different (P=0.192-0.315) between the PG (total 1.29±0.37 degrees/mo, 0.71±0.23 degrees/mo at distal femur, 0.59±0.16 degrees/mo at proximal tibia, n=19) and the SG (total 1.22±0.49 degrees/mo, 0.65±0.25 degrees/mo at distal femur, 0.57±0.23 degrees/mo at proximal tibia, n=49). The magnitude of rebound phenomenon in the PG (4.1±1.9 degrees) was greater (P<0.001) than that in the SG (1.1±3.1 degrees). The use of plates and faster correction speed, rather than more severe preoperative deformity or greater correction angle, were positively associated with the rebound phenomenon in regression analyses. Among the 68 knees, 1 showed valgus alignment ≥5 degrees and 5 showed varus alignment ≥5 degrees at the last follow-up. All the 6 cases were observed in the SG. Surgical wound dehiscence was observed in 1 patient in the PG.

Conclusions:

The use of plates and faster correction speed were positively associated with the rebound phenomenon. Careful attention will be needed with the corresponding conditions for optimal results. Progressive genu varum after transphyseal screw removal, which was observed in this study, should be explored in future research.

Level of Evidence:

Level III—retrospective comparative series.
Cancer statistics in China and United States, 2022: profiles, trends, and determinants
Authors: Xia Changfa , Dong Xuesi , Li He , Cao Maomao , Sun Dianqin , He Siyi , Yang Fan , Yan Xinxin , Zhang Shaoli , Li Ni , Chen Wanqing
Published: February 2022

Background:

The cancer burden in the United States of America (USA) has decreased gradually. However, China is experiencing a transition in its cancer profiles, with greater incidence of cancers that were previously more common in the USA. This study compared the latest cancer profiles, trends, and determinants between China and USA.

Methods:

This was a comparative study using open-source data. Cancer cases and deaths in 2022 were calculated using cancer estimates from GLOBOCAN 2020 and population estimates from the United Nations. Trends in cancer incidence and mortality rates in the USA used data from the Surveillance, Epidemiology, and End Results program and National Center for Health Statistics. Chinese data were obtained from cancer registry reports. Data from the Global Burden of Disease 2019 and a decomposition method were used to express cancer deaths as the product of four determinant factors.

Results:

In 2022, there will be approximately 4,820,000 and 2,370,000 new cancer cases, and 3,210,000 and 640,000 cancer deaths in China and the USA, respectively. The most common cancers are lung cancer in China and breast cancer in the USA, and lung cancer is the leading cause of cancer death in both. Age-standardized incidence and mortality rates for lung cancer and colorectal cancer in the USA have decreased significantly recently, but rates of liver cancer have increased slightly. Rates of stomach, liver, and esophageal cancer decreased gradually in China, but rates have increased for colorectal cancer in the whole population, prostate cancer in men, and other seven cancer types in women. Increases in adult population size and population aging were major determinants for incremental cancer deaths, and case-fatality rates contributed to reduced cancer deaths in both countries.

Conclusions:

The decreasing cancer burden in liver, stomach, and esophagus, and increasing burden in lung, colorectum, breast, and prostate, mean that cancer profiles in China and the USA are converging. Population aging is a growing determinant of incremental cancer burden. Progress in cancer prevention and care in the USA, and measures to actively respond to population aging, may help China to reduce the cancer burden.
Exploring attendance at emergency departments for children with non-urgent conditions in Turkey: a qualitative study of parents and healthcare staff perspectives
Authors: Butun Ahmet , Lynn Fiona , McGaughey Jennifer , McLaughlin Katrina , Linden Mark
Published: February 2022

Background:

Overcrowding in Emergency Departments (EDs) is a significant global concern with negative consequences for patients, healthcare staff, and healthcare systems. The use of EDs by parents of children with non-urgent conditions is associated with overcrowding, higher healthcare costs, lower quality of care, and longer waiting times. Research in this area has largely been conducted in high-income countries, with a dearth of work originating in middle and low-income regions. The aim of this study was to explore the reasons for parents attending EDs with their child for non-urgent conditions in Turkey.

Method:

Semi-structured interviews were conducted with 13 parents, 15 ED staff, and 10 General Practitioners (GPs) in 2 regions of Turkey between March and May 2017. Data were analyzed using the principles of grounded theory.

Results:

The findings were classified into 5 core categories: (1) parents’ feelings, knowledge, and perceived inability to provide self-care; (2) perceived limitations of healthcare services, system, and staff; (3) parents’ preferences for hospital and ED services; (4) adverse impact on ED services; and (5) perceived needs for care.

Conclusion:

This is the first study conducted in a middle-income country regarding parental reasons for using the ED for nonurgent conditions. Greater efforts must be made to reduce unnecessary visits to the ED to better meet service user needs and to increase the satisfaction of both parents and healthcare staff. The findings of this study may inform healthcare providers, policymakers, healthcare staff, and researchers to design interventions in order to mitigate overcrowding in the ED.
Association of arterial stiffness with coronary artery calcium score in the general-population: the Swedish CArdioPulmonary bioImage study
Authors: Muhammad Iram Faqir , Engvall Jan E. , Persson Margaretha , Borné Yan , Nilsson Peter M. , Östgren Carl Johan , Engström Gunnar
Published: February 2022

Objectives:

Coronary artery calcium score (CACS) is a marker of subclinical atherosclerosis. However, there is little data related to the association between arterial stiffness and CACS in the general population. The aim of this study was to explore the association between carotid femoral-pulse wave velocity (c-f PWV), a widely accepted marker of arterial stiffness, and CACS.

Methods:

Participants with complete measurements on c-f PWV, CACS and confounding variables from the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort were included in the final study population (n = 8725). CACS was divided into three categories (<10, >10 and ≤100, and >100) and multinomial logistic regression was performed to explore the association between these categories of CACS and quartiles of c-f PWV, and for per one standard deviation (SD) increment of c-f PWV.

Results:

CACS ≤10, >10 and ≤100, and >100 were present in 69.3, 17.8 and 12.9% of the study population, respectively. The odds ratio (OR) for CACS >100 for the fourth quartile (Q4) of c-f PWV vs. Q1 (reference category) was 1.62 (95% confidence interval [CI] 1.25–2.12) after adjustments. One standard deviation increase in c-f PWV was independently associated with a higher odds of having a CACS category >100 (OR: 1.25, 95% CI 1.14–1.36) in the final multivariable model.

Conclusion:

c-f PWV is positively associated with increased risk of higher CACS, and can be valuable in identifying individuals at risk for sub-clinical atherosclerosis.

Graphical abstract:

http://links.lww.com/HJH/B863.
The impact of maternal hyperglycaemia first detected in pregnancy on offspring blood pressure in Soweto, South Africa
Authors: Boerstra Brittany A. , Soepnel Larske M. , Nicolaou Veronique , Kolkenbeck-Ruh Andrea , Kagura Juliana , Ware Lisa J. , Norris Shane A. , Klipstein-Grobusch Kerstin
Published: February 2022

Background:

The long-term consequences for offspring born to mothers with hyperglycaemia first detected in pregnancy (HFDP) are not yet well understood and its influence on childhood blood pressure has not previously been assessed in sub-Saharan Africa.

Objective:

The objective of this study was to evaluate the association between maternal HFDP and offspring blood pressure in 3 to 6-year-old children in Soweto, South Africa.

Methods:

Oscillometric blood pressure was measured in 189 children born to mothers with and without HFDP diagnosed by 75 g 2-h oral glucose tolerance test. The 2017 AAP Guidelines for Childhood Hypertension were used as reference standard, and the term ‘elevated blood pressure’ referred to blood pressure readings above the 90th percentile for age, height and sex. The association between maternal HFDP and offspring blood pressure was analysed using multivariable linear regression.

Results:

Elevated blood pressure was identified in 49.7% of children. Maternal hyperglycaemia was not associated with offspring blood pressure when adjusted for offspring age, height and sex (SBP: 0.199, P 
= 0.888; DBP: 0.185, P 
= 0.837) or after multivariable adjustment (SBP: –0.286, P = 0.854; DBP: 0.215, P = 0.833). In the full model for SBP, child BMI age z-score was a significant predictor of blood pressure at 3–6years (1.916, P = 0.008).

Conclusion:

Although maternal HFDP was not associated with childhood blood pressure at 3–6 years, the prevalence of elevated blood pressure in this group of preschool-aged children is concerning. Future research is needed to further evaluate childhood obesity as a modifiable risk factor to reduce hypertension and cardiovascular risk in an African setting.
Acute liver failure
Authors: Vasques Francesco , Cavazza Anna , Bernal William
Published: February 2022

Purpose of review

Present an outline of acute liver failure, from its definition to its management in critical care, updated with findings of selected newer research.

Recent findings

Survival of patients with acute liver failure has progressively improved. Intracranial hypertension complicating hepatic encephalopathy is now much less frequent than in the past and invasive ICP monitoring is now rarely used. Early renal replacement therapy and possibly therapeutic plasma exchange have consolidated their role in the treatment. Further evidence confirms the low incidence of bleeding in these patients despite striking abnormalities in standard tests of coagulation and new findings of abnormalities on thromboelastographic testing. Specific coagulopathy profiles including an abnormal vWF/ADAMTS13 ratio may be associated with poor outcome and increased bleeding risk. Use of N-acetylcysteine in nonparacetamol-related cases remains unsupported by robust clinical evidence. New microRNA-based prognostic markers to select patients for transplantation are described but are still far from widespread clinical applicability; imaging-based prognostication tools are also promising. The use of extracorporeal artificial liver devices in clinical practice is yet to be supported by evidence.

Medical treatment of patients with acute liver failure is now associated with significantly improved survival. Better prognostication and selection for emergency liver transplant may further improve care for these patients.
Implications and effects of COVID-19 on diagnosis and management of prostate cancer
Authors: Chan Vinson Wai-Shun , Asif Aqua , Koe Jasmine Sze-Ern , Ng Alexander , Ng Chi Fai , Teoh Jeremy Yuen-Chun
Published: February 2022

Purpose of review

The Coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty on the optimal management for prostate cancer (PCa). This narrative review aims to shed light on the optimal diagnosis and management of patients with or suspected to have PCa.

Recent findings

Faecal-oral or aerosol transmission is possible during prostate procedures; caution must be in place when performing digital rectal examinations, transrectal ultrasound-guided prostate biopsies and prostate surgeries requiring general anaesthesia. Patients must also be triaged using preoperative polymerase chain reaction tests for COVID-19. COVID-19 has accelerated the adoption of multiparametric Magnetic Resonance Imaging (MRI), reducing the need for prostate biopsy unless when absolutely indicated, and the risk of COVID-19 spread can be reduced. Combined with prostate-specific antigen (PSA) density, amongst other factors, multiparametric MRI could reduce unnecessary biopsies in patients with little chance of clinically significant PCa. Treatment of PCa should be stratified by the risk level and preferences of the patient. COVID-19 has accelerated the development of telemedicine and clinicians should utilise safe and effective teleconsultations to protect themselves and their patients.

COVID-19 transmission during prostate procedures is possible. Patients with a Prostate Imaging-Reporting and Data System (PI-RADS) of <3 and PSA density <0.15 ng/ml/ml are deemed low-risk and are safe to undergo surveillance without MRI-targeted biopsy. Intermediate- or high-risk patients should be offered definitive treatment within four months or 30days of diagnosis to avoid compromising treatment outcomes; three-month courses of neoadjuvant androgen deprivation therapy can be considered when a delay of surgery is anticipated.
Baseline HIV drug-resistance testing: 12 US jurisdictions, 2014–2019
Authors: Hugueley Brandon , McClung Robert P. , Saduvala Neeraja , Oster Alexandra M. , France Anne Marie
Published: February 2022

Objective:

To understand recent patterns in reported baseline HIV drug-resistance testing over time in the United States.

Design:

Data from the National HIV Surveillance System for persons who were aged at least 13 years at the time of HIV diagnosis during 2014–2019 and resided in one of 12 US jurisdictions with high levels of reporting in 2014 and 2015.

Methods:

Among persons included in the analysis, we calculated the total proportion of HIV diagnoses occurring during 2014–2019 with a reported baseline sequence by year of diagnosis and sequence type. A baseline sequence was defined as any protease/ reverse transcriptase (PR/RT) or integrase sequence generated from a specimen collected 90 days or less after diagnosis.

Results:

During 2014–2019, reported levels of baseline PR/RT (with or without integrase) testing varied by year from 46.9% to 51.8% without any clear pattern over time. PR/RT with integrase testing increased (8.3–19.4%) and integrase-only testing remained low (1.9–1.3%).

Conclusion:

While reported levels of baseline PR/RT (with or without integrase) testing have remained sufficiently high for the purposes of molecular cluster detection, higher levels would strengthen jurisdictions’ and the Centers for Disease Control and Prevention's ability to monitor trends in HIV drug-resistance and detect and respond to HIV molecular clusters. Efforts to increase levels of reported baseline testing likely need to address both gaps in testing as well as reporting.
Intraductal Papilloma With Carcinoma of the Breast Described by Dedicated Breast 18F-FDG PET
Authors: Noritake Mutsumi , Yamada Akimitsu , Yamanaka Shoji , Utsunomiya Daisuke , Inoue Tomio
Published: February 2022

Intraductal papilloma (IDP) is a benign tumor of the breast. However, IDP has been reported to show high uptake of 18F-FDG using whole-body PET. We experienced IDP with low-grade ductal carcinoma in situ using dedicated breast PET, which is more sensitive than whole-body PET. The 18F-FDG uptake of the whole tumor was high, and differentiation between the carcinoma and the residual benign lesion was difficult. This is the first report of IDP detected with dedicated breast PET. Diagnosis of IDP is sometimes controversial; papilloma may show glucose uptake similar to that of low-grade carcinoma.
Axillary Anatomy and Pathology
Authors: Stowell Justin T. , McComb Barbara L. , Mendoza Dexter P. , Cahalane Alexis M. , Chaturvedi Abhishek
Published: February 2022

The axilla contains several important structures which exist in a relatively confined anatomic space between the neck, chest wall, and upper extremity. While neoplastic lymphadenopathy may be among the most common axillary conditions, many other processes may be encountered. For example, expanded use of axillary vessels for access routes for endovascular procedures will increase the need for radiologists to access vessel anatomy, patency, and complications that may arise. Knowledge of axillary anatomy and pathology will allow the imager to systematically evaluate the axillae using various imaging modalities.
Antidepressant drug use and regional prescribing patterns in Germany: results from a large population-based study
Authors: Dörks Michael , Hoffmann Falk , Jobski Kathrin
Published: February 2022

Objective

To consider antidepressant prescribing on a population level with a focus on regional prescribing patterns in Germany.

Basic methods

Based on data from about 70 million individuals covered by all statutory health insurance funds in Germany in 2010, the prevalence of antidepressant use (overall, for drug classes and individual drugs) was calculated stratified by age and sex. Regional analyses were performed on a state and also on a district level.

Main results

The study population comprised 68 427 464 (female: 53.0%) persons, of which 5 052 293 (7.4%) were prescribed at least one antidepressant. The most frequently prescribed drug class was tricyclic antidepressants whereas on a substance level citalopram was most commonly used. Antidepressant prescribing was lowest in children and adolescents (0.2%) and most common in persons aged 70 years and older (13.4%). Women more often received antidepressants than men (9.7% vs. 4.8%). Prevalence of antidepressant use varied between 8.7% (Saarland) and 6.3% (Saxony-Anhalt) and was generally highest in the southwestern and lowest in the eastern states. Accordingly, districts with the highest prevalence were located in the southwestern states.

Principal conclusions

Antidepressant use in Germany varied considerably by age and sex and also on a state and district level.
Lactobacillus huangpiensis sp. nov. and Lactobacillus laiwuensis sp. nov., isolated from the gut of honeybee (Apis mellifera)
Authors: Li Ting Ting , Gu Chun Tao
Published: February 2022

Four Gram-stain-positive bacterial strains were isolated from the gut of honeybee (Apis mellifera) in China. These strains were characterized using a polyphasic taxonomic approach. The data demonstrated that three of the four strains represented two novel species of the genus

Lactobacillus

, strains F306-1T and F551-2T were designated as the type strains. Results of 16S rRNA gene sequence analysis indicated that strains F306-1T, F447 and F551-2T were phylogenetically related to the type strains of

Lactobacillus kimbladii

and

Lactobacillus kullabergensis

, having 99.1–99.7 % 16S rRNA gene sequence (about 1400 bp) similarities. The phylogenetic tree based on concatenated pheS, rpoA, gyrB, hsp60, recA, rpoB and tuf sequences (4114 bp) and the phylogenomic tree based on whole genome sequences indicated that strains F306-1T and F447 were most closely related to

L. kullabergensis

Biut2NT, and strain F551-2T was most closely related to

L. kimbladii

Hma2NT. Strains F306-1T and F447 shared 99.9 % average nucleotide identity (ANI), 99.7 % digital DNA–DNA hybridization (dDDH) and 99.9 % average amino acid identity (AAI) values, indicating that they belong to the same species. Strain F306-1T exhibited the highest ANI (94.4 %), dDDH (56.7 %) and AAI (94.7 %) values to

L. kullabergensis

Biut2NT. Strain F551-2T had the highest ANI (94.0 %), dDDH (54.3 %) and AAI (95.8 %) values with

L. kimbladii

Hma2NT. Acid production from amygdalin, maltose, starch, gentiobiose and turanose, activity of esterase (C4) and α-glucosidase, growth with 3 % NaCl at 37 °C under strict anaerobic condition (on mMRS agar plates), and growth with 1–6% NaCl at 37 °C under aerobic condition (on mMRS agar plates supplemented with 0.05 % cysteine or with 1 % cysteine and 2 % fructose) could differentiate strains F306-1T and F447 from

L. kullabergensis

DSM 26262T. Acid production from d-glucose, arbutin and gentiobiose, growth with 3 % NaCl at 37 °C under strict anaerobic condition (on mMRS agar plates), and growth at 45 °C under strict anaerobic condition (on mMRS agar plates) could differentiate strain F551-2T from

L. kimbladii

DSM 26263T. Based upon the data obtained in the present study, two novel species, Lactobacillus huangpiensis sp. nov. and Lactobacillus laiwuensis sp. nov., are proposed and the type strains are F306-1T (=LMG 32144T=JCM 34361T=CCTCC AB 2020300T) and F551-2T (=JCM 34502T=CCTCC AB 2021027T), respectively.
Towards comprehensive understanding of bacterial genetic diversity: large-scale amplifications in Bordetella pertussis and Mycobacterium tuberculosis
Authors: Abrahams Jonathan S. , Weigand Michael R. , Ring Natalie , MacArthur Iain , Etty Joss , Peng Scott , Williams Margaret M. , Bready Barret , Catalano Anthony P. , Davis Jennifer R. , Kaiser Michael D. , Oliver John S. , Sage Jay M. , Bagby Stefan , Tondella M. Lucia , Gorringe Andrew R. , Preston Andrew
Published: February 2022

Bacterial genetic diversity is often described solely using base-pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplication/amplifications are thought to be widespread among bacteria but due to their often-intractable size and instability, comprehensive studies of these mutations are rare. We define a methodology to investigate amplifications in bacterial genomes based on read depth of genome sequence data as a proxy for copy number. We demonstrate the approach with

Bordetella pertussis

, whose insertion sequence element-rich genome provides extensive scope for amplifications to occur. Analysis of data for 2430

B. pertussis

isolates identified 272 putative amplifications, of which 94 % were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of amplifications, suggesting unstable and sporadic characteristics. Genome instability was further described in vitro using long-read sequencing via the Nanopore platform, which revealed that clonally derived laboratory cultures produced heterogenous populations rapidly. We extended this research to analyse a population of 1000 isolates of another important pathogen,

Mycobacterium tuberculosis

. We found 590 amplifications in

M. tuberculosis

, and like

B. pertussis

, these occurred primarily at hotspots. Genes amplified in

B. pertussis

include those involved in motility and respiration, whilst in M. tuberuclosis, functions included intracellular growth and regulation of virulence. Using publicly available short-read data we predicted previously unrecognized, large amplifications in

B. pertussis

and

M. tuberculosis

. This reveals the unrecognized and dynamic genetic diversity of

B. pertussis

and

M. tuberculosis

, highlighting the need for a more holistic understanding of bacterial genetics.
First genetic data for the Critically Endangered Cuban endemic Zapata RailCyanolimnas cerverai, and the taxonomic implications
Authors: Brown Alex F. , Shannon Thomas J. , Collinson J. Martin , Kirwan Guy M. , Kirkconnell Arturo , Stervander Martin
Published: February 2022

The taxonomic affinity of the near-flightless Zapata RailCyanolimnas cerverai, a Critically Endangered and highly localized species endemic to Cuba, has long been debated. Morphological analyses have suggested that this species, which constitutes a monotypic genus, could be related either to the extinct Tahitian Cave Rails (Nesotrochissp.) or to the South American rail tribe Pardirallini, i.e., the generaNeocrex, Mustelirallus, andPardirallus. Whilst pronounced phenotypic convergence–and divergence–among rails have repeatedly proven morphology-based phylogenies unreliable, thus far no attempt to sequence DNA from the enigmaticCyanolimnashas succeeded. In this study, we extracted historic DNA from a museum specimen collected in 1927 and sequenced multiple short fragments that allowed us to assemble a partial sequence of the mitochondrial cytochrome oxidase I gene. Phylogenetic analyses confirm thatCyanolimnasbelongs in tribe Pardirallini as sister to genusNeocrex, from which it diverged about six million years ago. Their divergence fromMusteliralluswas estimated at about eight million years ago. Based on morphology and our mitochondrial phylogeny, we conclude that it is unjustified to retain the monotypic genusCyanolimnasand tentatively recommend thatC. cerveraiand the twoNeocrexspecies are ascribed to genusMustelirallus.

Abstract Figure
Using cGMP analogues to modulate photoreceptor light sensitivity: Perspectives for the treatment of retinal degeneration
Authors: Wucherpfennig Sophie , Haq Wadood , Popp Valerie , Kesh Sandeep , Das Soumyaparna , Melle Christian , Rentsch Andreas , Schwede Frank , Paquet-Durand François , Nache Vasilica
Published: February 2022

Cyclic nucleotide-gated (CNG) channels play an essential role within the phototransduction cascade in vertebrates. Although rod and cone light responses are mediated through similar pathways, each photoreceptor type relies on a specific CNG-channel isoform. In many forms of retinal degeneration, increased cGMP levels initiate a pathophysiological rollercoaster, which starts with an enhanced CNG-channel activation, often in rod photoreceptors. This causes cell death of both rods and cones, and eventually leads to complete blindness. Unfortunately, the targeting of the desired channel isoform still constitutes the bottleneck for many therapeutic schemes.

Here, we present a novel strategy, based on cGMP analogues with opposite types of action, which allows for the selective modulation of either rod or cone photoreceptors. A combined treatment with a weak rod-selective CNG-channel inhibitor (Rp-8-Br-PET-cGMPS) and a cone-selective CNG-channel activator (8-pCPT-cGMP) preserved the normal CNG-channel function at physiological and pathological cGMP levels. The effectiveness of this approach was tested and confirmed in explanted mouse retina. Under physiological conditions, the inhibitor silenced the rods selectively and decreased the dependency of cone responses on light intensity. Remarkably, the activator, when applied together with the inhibitor, reinstated only the light responsiveness of cones. Yet, when applied alone, the activator dampened rod responses more strongly than those of cones.

Hence, combinations of cGMP analogues with desired properties may elegantly address the isoform-specificity problem in future pharmacological therapies. Beyond therapies for retinal degeneration diseases, treatments based on this strategy may allow modulation of visual performance in certain light environments or disease conditions.

One Sentence Summary

A combination of cGMP analogues with opposite types of action can selectively modulate either rod or cone photoreceptor function.