bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambulatory blood pressure and hypertension control in children with autosomal recessive polycystic kidney disease: clinical experience from two central European tertiary centres
Authors: Seeman Tomáš , Blažík Radek , Fencl Fencl , Bláhová Květa , Obeidová Lena , Štekrová Jitka , Weigel Friederike , John-Kroegel Ulrike
Published: January 2022

Objective

: Arterial hypertension is a common complication in patients with autosomal recessive polycystic kidney disease (ARPKD), occurring in 33–75% of children when measured by office blood pressure (OBP). Ambulatory blood pressure monitoring (ABPM) is a superior tool for investigating blood pressure relative to OBP. The aim of our study was to investigate the prevalence and control of hypertension in children with ARPKD based on ABPM.

Methods:

This retrospective study evaluated 36 children with ARPKD and at least one ABPM performed in two our tertiary paediatric nephrology centres and 29 children with at least two ABPM. Ambulatory hypertension was defined as mean daytime or night-time BP at least 95th percentile or use of antihypertensives and controlled hypertension as normal ambulatory BP in children on antihypertensive drugs.

Results:

The first ABPM study revealed ambulatory hypertension in 94% of children. Untreated or uncontrolled ambulatory hypertension was diagnosed in 67% and controlled hypertension in only 28%. Masked hypertension was found in 5.5% and white-coat hypertension in 14%. The last ABPM study revealed ambulatory hypertension in 86% (all 86% hypertensive children on drugs, i.e. no untreated hypertension), the prevalence of controlled hypertension increased to 59%. Masked hypertension was detected in 8.3% and white-coat hypertension in 10%. Ambulatory blood pressure correlated neither with kidney length nor with glomerular filtration rate. Echocardiography demonstrated left ventricular hypertrophy (LVH) in 27% of children at the time of their first ABPM.

Conclusion:

The prevalence of ambulatory hypertension is very high in children with ARPKD, while the control of hypertension improves over time.
Effects of hypnosis vs mindfulness meditation vs education on chronic pain intensity and secondary outcomes in veterans: a randomized clinical trial
Authors: Williams Rhonda M. , Day Melissa A. , Ehde Dawn M. , Turner Aaron P. , Ciol Marcia A. , Gertz Kevin J. , Patterson David , Hakimian Shahin , Suri Pradeep , Jensen Mark P.
Published: January 2022

Effective, rigorously evaluated nonpharmacological treatments for chronic pain are needed. This study compared the effectiveness of training in hypnosis (HYP) and mindfulness meditation (MM) with an active education control (ED). Veterans (N = 328) were randomly assigned to 8 manualized, group-based, in-person sessions of HYP (n = 110), MM (n = 108), or ED (n = 110). Primary (average pain intensity [API]) and secondary outcomes were assessed at pretreatment, posttreatment, and 3 and 6 months posttreatment. Treatment effects were evaluated using linear regression, a generalized estimating equation approach, or a Fisher exact test, depending on the variable. There were no significant omnibus between-group differences in pretreatment to posttreatment change in API; however, pretreatment to posttreatment improvements in API and several secondary variables were seen for participants in all 3 conditions. Participation in MM resulted in greater decreases in API and pain interference at 6 months posttreatment relative to ED. Participation in HYP resulted in greater decreases in API, pain interference, and depressive symptoms at 3 and 6 months posttreatment compared with ED. No significant differences on outcomes between HYP and MM were detected at any time point. This study suggests that all 3 interventions provide posttreatment benefits on a range of outcomes, but the benefits of HYP and MM continue beyond the end of treatment, while the improvements associated with ED dissipate over time. Future research is needed to determine whether the between-group differences that emerged posttreatment are reliable, whether there are benefits of combining treatments, and to explore moderating and mediating factors.
Enlargement of Eustachian Tube Lumen in Patulous Eustachian Tube Patients Compared to that by Aging
Authors: Ikeda Ryoukichi , Kusano Yusuke , Kawamura Yoshinobu , Oshima Hidetoshi , Kikuchi Toshiaki , Kawase Tetsuaki , Katori Yukio , Kobayashi Toshimitsu
Published: January 2022

Objective:

To evaluate the Eustachian tube (ET) dimensions in patulous ET (PET) patients compared with that by aging using sitting 3D computed tomography (CT).

Study Design:

Retrospective study.

Setting:

Tertiary referral center.

Subjects and methods:

A retrospective survey of medical records in Sen-En Rifu Hospital identified 105 ears of 76 PET patients and 65 ears of 34 patients without ET dysfunction findings (non-PET). Subjects in both PET and non-PET groups were then divided into two age groups. Groups A and C defined as non-PET and PET subjects respectively, who were under the age of 60 years, while Groups B and D defined of non-PET and PET subjects respectively, who were 60 years and above. 3D CT (Accuitomo; Morita, Kyoto, Japan) was performed on all subjects in the sitting position. The ET lumen from the ET pharyngeal orifice to 15 mm was analyzed.

Results:

No significant difference in the ET lumen near the pharyngeal orifice was found between Group A and C; however, there was a significant difference in the ET at points lateral to the pharyngeal orifice. The ET lumen was significantly larger at the site close to the pharyngeal orifice in Group B as compared to that of Group A. For the two groups of PET classified according to the size of the pharyngeal orifice and area close to the isthmus, age was only significantly different between two groups of pharyngeal orifice. On the contrary, sonotumometry and Ohta method were significantly different between the two groups of the area close to the isthmus.

Conclusion:

The lumen of the ET is enlarged in both PET and aging. However, the responsible site was found to be different. While the enlargement of the ET lumen in 60 years and above subjects without PET mainly occurred near the pharyngeal orifice of the ET, it was near the isthmus in under 60 years PET patients. Further study of possible clinical implications of these findings as well as treatment strategy are required.
Association between coronary artery calcium score and in-stent restenosis after drug-eluting stent implantation
Authors: Zheng Xiaowen , Xu Ke , Yang Xiaoxiao , Yang Wentao , Zhang Weifeng , Jiang Yue , Zhang Yipeng , Qiu Xingbiao , Shi Hongyu , Jiang Lisheng , Shen Linghong , He Ben
Published: January 2022

Background

Coronary artery calcium (CAC) is a modifiable contributor of in-stent restenosis (ISR), but quantitative analyses using a noninvasive approach are limited. We aimed to investigate the associations between CAC score derived from ECG-gated coronary computed tomography angiography (CCTA) or non-gated non-contrast chest computed tomography (NCCT) and ISR.

Methods

We included 368 lesions in 194 patients with coronary drug-eluting stent implantations in final analyses. CAC was quantified using the Agatston score. Primary endpoint was ISR, defined as lumen diameter stenosis over 50% at the stent segment or its proximal or distal edges (5-mm segments adjacent to the stent), at angiographic follow-up.

Results

The CAC scores in either CCTA/2.5 mm group (r = 0.7702; P < 0.0001) or NCCT/5 mm group (r = 0.7105; P < 0.0001) were both correlated with in-stent diameter stenosis. The receiver-operating characteristic curve analysis identified a CAC score >245 in CCTA/2.5 mm group as the optimal ISR cutoff (sensitivity, 60.0%; specificity, 83.7%; area under the curve, 0.744; P < 0.001), and >209 in NCCT/5 mm group (sensitivity, 46.7%; specificity, 91.9%; area under the curve, 0.704; P < 0.001). Multivariable logistic regression models indicated a CAC score >245 in CCTA/2.5 mm group and >209 in NCCT/5 mm group independently associated with an 8.46- and 21.89-fold increase in ISR, respectively (all P < 0.01).

Conclusions

Either a CAC score >245 in CCTA/2.5 mm or >209 in NCCT/5 mm was significantly associated with increased risk in ISR.
Acute traumatic brain injury in frail patients: the next pandemic
Authors: Baggiani Marta , Guglielmi Angelo , Citerio Giuseppe
Published: January 2022

Purpose of review

To highlight recent findings on the evaluation and impact of frailty in the management of patients with traumatic brain injury (TBI).

Recent findings

Frailty is not a direct natural consequence of aging. Rather, it commonly results from the intersection of age-related decline with chronic diseases and conditions. It is associated with adverse outcomes such as institutionalization, falls, and worsening health status. Growing evidence suggests that frailty should be a key consideration both in care planning and in adverse outcome prevention. The prevalence of elderly patients with TBI is increasing, and low-energy trauma (i.e., ground or low-level falls, which are typical in frail patients) is the major cause. Establishing the real incidence of frailty in TBI requires further studies. Failure to detect frailty potentially exposes patients to interventions that may not benefit them, and may even harm them. Moreover, considering patients as ‘nonfrail’ purely on the basis of their age is unacceptable. The future challenge is to shift to a new clinical paradigm characterized by more appropriate, goal-directed care of frail patients.

The current review highlights the crucial importance of frailty evaluation in TBI, also given the changing epidemiology of this condition. To ensure adequate assessment, prevention and management, both in and outside hospital, there is an urgent need for a valid screening tool and a specific frailty-based and comorbidity-based clinical approach.
Distant metastasis from head and neck cancer: role of surgical treatment
Authors: Vartanian Jose Guilherme , Gross Jefferson Luis , Kowalski Luiz Paulo
Published: January 2022

Purpose of review

The rates of distant metastases in patients with head and neck squamous cell carcinoma varies from 3 to 50%. Metastases are usually multiple, diagnosed within 24 months after treatment and sited in the lungs, bone or liver. This review highlights the importance of a personalized treatment approach in such patients.

Recent findings

In patients with primary tumor controlled and with oligometastatic disease, surgical options can be considered, especially for lung metastases. Overall survival for patients who are candidates for lung metastasectomy can be as high as 59%. In bone and liver metastases, resection is not frequently used but radiofrequency ablation is a promising option. Finally, mediastinal and axillary lymph node metastasis are classified as distant metastases, and lymph node dissection is the treatment of choice whenever the disease is limited to these sites.

Patients with distant metastases usually are considered incurable; however, an aggressive local treatment of solitary distant metastases should be considered in highly selected patients, with a potential increase of overall survival.
Assessment of the Educational and Health Care System–Related Issues From Physicians' and Nurses' Perspectives Before Developing a Palliative Care Program Within the Palestinian Health Care System
Authors: Abu-Odah Hammoda , Molassiotis Alex , Liu Justina Yat Wa
Published: January 2022

A scarcity in research assessing the palliative care (PC) educational and health care system–related issues has been reported in the Middle East region; the region comprises a wide range of economically diverse countries. Discrepancies across countries have created difficulties in adopting other countries' experiences. This study aimed to assess PC knowledge, attitude, educational needs, and health care system–related issues from physicians' and nurses' perspectives before developing PC services within the Palestinian health care system. One hundred sixty-nine professionals participated in this cross-sectional survey. Data were collected by validated instruments. Professionals had insufficient knowledge about PC, but they had positive attitudes toward end-of-life care and care of the dying. Patients'/families' avoidance of talking about issues around dying and lack of training for staff related to PC were the most 2 significant barriers to providing PC. Educational level and previous training were found to be associated significantly with knowledge and attitudes toward PC. Study conclusions support the recommendation for integration of education about PC within the health curricula and in-service training and should cover the basic and advanced principles of PC and symptom management.
Dealing With Disordered Eating Thoughts and Behaviors in Youth
Authors: Jaeger Jessica L. , Isoldi Kathy K. , Salvatore Deborah , Burrowes Jerrilynn D.
Published: January 2022

Youth are vulnerable to societal pressures to be thin and are at higher risk of dieting to reduce body weight. Dieting can evolve into maladaptive behaviors intended to result in weight loss (disordered eating) because eating behaviors occur on a spectrum. This review is designed to assist clinicians in identifying and addressing disordered eating thoughts and behaviors in youths. Clinicians should rely on recognizing language describing disordered eating thoughts and behaviors, rather than on the youth's weight, when screening for disordered eating. Referral to specialized clinicians is crucial to guide the youth in developing a healthy relationship with food.
Digital Eyestrain and the Critical Fusion Frequency
Authors: Yan Keying , Rosenfield Mark
Published: January 2022

SIGNIFICANCE

Although the high prevalence of digital eyestrain has been well established, to date, there is no objective measurement of this condition. Previous studies have suggested that digital eyestrain may be associated with decreased critical fusion frequency, but the published evidence to support this association is sparse.

PURPOSE

This study sought to determine whether symptoms of digital eyestrain after a sustained computer task are indeed associated with changes in critical fusion frequency.

METHODS

The experiment was performed on 30 young visual-normal subjects. They attended two sessions, during which they undertook a 20-minute reading task. This comprised either reading random words from a tablet computer or a story from a printed children's book. Critical fusion frequency was measured both before and immediately after each of the reading tasks. In addition, the level of digital eyestrain was assessed by subjects completing a questionnaire regarding ocular and visual symptoms experienced during each of the reading trials.

RESULTS

The mean increase in digital eyestrain symptoms after the digital and printed conditions was 11.37 (standard error of the mean [SEM], 2.23) and 4.40 (SEM, 1.34), respectively. Both the post-task symptom change (P < .001) and the difference between the two reading conditions (P = .004) were significant. The mean change in critical fusion frequency after the digital and printed conditions was −0.42 (SEM, 0.25) and −0.72 (SEM, 0.26), respectively. Neither the post-task change nor the difference between the two reading conditions was significant. In addition, when considering the digital condition only, no significant correlation was observed between the changes in critical fusion frequency and reported symptoms.

CONCLUSIONS

These results do not support the proposal that changes in critical fusion frequency can be used as an objective measure of eyestrain or other symptoms of digital eyestrain.
The Impact of Ineffective Esophageal Motility on Patients Undergoing Magnetic Sphincter Augmentation
Authors: Baison George N. , Jackson Anee S. , Wilshire Candice L. , Bell Reginald C. W. , Lazzari Veronica , Bonavina Luigi , Ayazi Shahin , Jobe Blair A. , Schoppmann Sebastian F. , Dunn Colin P. , Lipham John C. , Dunst Christy M. , Farivar Alexander S. , Bograd Adam J. , Louie Brian E.
Published: January 2022

Objective:

To evaluate and characterize outcomes of MSA in patients with IEM.

Summary Background Data:

MSA improves patients with gastroesophageal reflux and normal motility. However, many patients have IEM, which could impact the outcomes of MSA and discourage use.

Methods:

An international, multi-institutional case control study of IEM patients undergoing MSA matched to normal patients was performed. Primary outcomes were new onset dysphagia and need for postoperative interventions.

Results:

A total of 105 IEM patients underwent MSA with matching controls. At 1 year after MSA: GERD-Health Related Quality of Life was similar; DeMeester scores in IEM patients improved to 15.7 and 8.5 in controls (P = 0.021); and normalization of the DeMeester score for IEM = 61.7% and controls = 73.1% (P = 0.079).

In IEM patients, 10/12 (83%) with preop dysphagia had resolution; 11/66 (17%) had new onset dysphagia and 55/66 (83%) never had dysphagia. Comparatively, in non-IEM patients, 22/24 (92%) had dysphagia resolve; 2/24 (8%) had persistent dysphagia; 7/69 (10%) had new onset dysphagia, and 62/69 (90%) never had dysphagia.

Overall, 19 (18%) IEM patients were dilated after MSA, whereas 12 (11%) non-IEM patients underwent dilation (P = 0.151). Nine (9%) patients in both groups had their device explanted.

Conclusions:

Patients with IEM undergoing MSA demonstrate improved quality of life and reduction in acid exposure. Key differences in IEM patients include lower rates of objective GERD resolution, lower resolution of existing dysphagia, higher rates of new onset dysphagia and need for dilation. GERD patients with IEM should be counselled about these possibilities.
Population-based Trends in Obesity and Kidney Transplantation Among Patients With End-stage Kidney Disease
Authors: Wakam Glenn K. , Sheetz Kyle H. , Gerhardinger Laura , Montgomery John R. , Waits Seth A.
Published: January 2022

Background.

Obesity is a barrier to transplant, reducing access and leading to worse outcomes versus nonobese adults. Most transplant centers in the United States maintain body mass index (BMI) cutoffs to listing for kidney transplantation of 35 to 40 kg/m2. There is little contemporary data on the prevalence of obesity among patients with end-stage kidney disease (ESKD) despite its impact on clinical outcomes and healthcare expenditures.

Methods.

We utilized data from the US Renal Data System from 2008 to 2016 to identify a prevalent cohort of 1 079 410 patients with ESKD. Linear regression determined trends in the proportion of patients within each category of BMI. We also evaluated geographic variation in rates of obesity and transplantation across the United States.

Results.

Among the 1 079 410 ESKD patients, the largest cohort of patients were those with obesity (n = 423 270; 39.2%). There were 309 707 (28.7%) patients with an overweight BMI and 274 683 (25.4%) with a normal BMI. The proportion of patients with obesity increased significantly from 36.8% in 2008 to 40.2% in 2016 (trend 0.28; 95% confidence interval, 0.05-0.51). There was significant geographic variation by state with rates of obesity ranging from 32.3% to 45.4% and state transplant rates among those obese patients ranging from 22.5% to 46.8%. There is a weak correlation between states with increased rates of obese ESKD patients and states with an increased obesity transplant rate as indicated with r = 0.40 (P = 0.003).

Conclusions.

Beneficiaries with obesity are now the largest and fastest growing demographic among patients with ESKD in the United States.
Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion
Authors: Xu Min , Zhou Fangyu , Ahmed Ola , Randle Lucy V. , Shin Jun-Kyu , Zhu Yuehui , Upadhya Gundumi A. , Byrnes Kathleen , Wong Brian , Kim Jae-Sung , Lin Yiing , Chapman William C.
Published: January 2022

Background.

Perfusate lactate clearance (LC) is considered one of the useful indicators of liver viability assessment during normothermic machine perfusion (NMP); however, the applicable scope and potential mechanisms of LC remain poorly defined in the setting of liver donation after circulatory death.

Methods.

The ex situ NMP of end-ischemic human livers was performed using the OrganOx Metra device. We further studied the extracellular signal-regulated kinases (phospho-extracellular signal-regulated kinase1/2 [pERK1/2]) pathway and several clinical parameters of these livers with successful LC (sLC, n = 5) compared with non-sLC (nLC, n = 5) in the perfusate (<2.2 mmol/L at 2 h, n = 5, rapid retrieval without normothermic regional perfusion).

Results.

We found the pERK1/2 level was substantially higher in the nLC livers than in the sLC livers (n = 5) at 2- and 6-h NMP (P = 0.035 and P = 0.006, respectively). Immunostaining showed that upregulation of pERK1/2 was in both the hepatocytes and cholangiocytes in the nLC livers. Successful LC was associated with a marginally higher glycogen restoration than nLC at 2 h NMP (n = 5, P = 0.065). Furthermore, bile lactate levels in all sLC livers were cleared into the normal range at 6 h NMP, whereas in the nLC group, only 2 livers had lower bile lactate levels, and the other livers had rising bile lactate levels in comparison with the corresponding perfusate lactate levels. The necrosis scores were higher in the nLC than in the sLC livers (n = 5) at 0- and 6-h NMP (P = 0.047 and P = 0.053, respectively).

Conclusions.

The dual LC in perfusate and bile can be helpful in evaluating the hypoxic injury of hepatocytes and cholangiocytes during the NMP of donation after circulatory death in liver donors.
Discordance Between SARS-CoV-2–specific Cell-mediated and Antibody Responses Elicited by mRNA-1273 Vaccine in Kidney and Liver Transplant Recipients
Authors: Fernández-Ruiz Mario , Almendro-Vázquez Patricia , Carretero Octavio , Ruiz-Merlo Tamara , Laguna-Goya Rocío , San Juan Rafael , López-Medrano Francisco , García-Ríos Estéfani , Más Vicente , Moreno-Batenero Miguel , Loinaz Carmelo , Andrés Amado , Pérez-Romero Pilar , Paz-Artal Estela , Aguado José María
Published: January 2022

Background.

Severe acute respiratory syndrome coronavirus 2–specific cell-mediated immunity (SARS-CoV-2-CMI) elicited by mRNA-based vaccines in solid organ transplant (SOT) recipients and its correlation with antibody responses remain poorly characterized.

Methods.

We included 44 (28 kidney, 14 liver, and 2 double organ) recipients who received the full series of the mRNA-1273 vaccine. SARS-CoV-2-CMI was evaluated at baseline, before the second dose, and at 2 wk after completion of vaccination by an ELISpot-based interferon-γ FluoroSpot assay using overlapping peptides covering the S1 domain. SARS-CoV-2 immunoglobulin G seroconversion and serum neutralizing activity against the spike protein were assessed at the same points by commercial ELISA and an angiotensin-converting enzyme-2/spike antibody inhibition method, respectively. Postvaccination SARS-CoV-2-CMI was compared with 28 healthcare workers who received the BNT162b2 vaccine.

Results.

Positive SARS-CoV-2-CMI increased from 6.8% at baseline to 23.3% after the first mRNA-1273 dose and 59.5% after the completion of vaccination (P < 0.0001). Lower rates were observed for immunoglobulin G seroconversion (2.3%, 18.6%, and 57.1%, respectively) and neutralizing activity (2.3%, 11.6%, and 31.0%). There was a modest correlation between neutralizing titers and the magnitude of SARS-CoV-2-CMI (Spearman’s rho: 0.375; P = 0.015). Fifteen recipients (35.7%) mounted SARS-CoV-2-CMI without detectable neutralizing activity, whereas 3 (7.1%) did the opposite, yielding poor categorical agreement (Kappa statistic: 0.201). Rates of positive SARS-CoV-2-CMI among SOT recipients were significantly decreased compared with nontransplant controls (82.1% and 100.0% after the first dose and completion of vaccination, respectively; P < 0.0001). Kidney transplantation, the use of tacrolimus and prednisone, and the number of immunosuppressive agents were associated with lower cell-mediated responses. Results remained unchanged when 3 recipients with prevaccination SARS-CoV-2-CMI were excluded.

Conclusions.

Two-thirds of SOT recipients mounted SARS-CoV-2-CMI following vaccination with mRNA-1273. Notable discordance was observed between vaccine-induced cell-mediated and neutralizing humoral immunities. Future studies should determine whether these patients with incomplete responses are effectively protected.
Hormonal and metabolic profiles of obese and nonobese type 2 diabetes patients: implications of plasma insulin, ghrelin, and vitamin D levels
Authors: Giha Hayder A. , AlDehaini Dhuha M. B. , Joatar Faris E. , Ali Muhalab E. , Al-Harbi Einas M. , Al Qarni Ali A.
Published: January 2022

Background

Type 2 diabetes (T2D) is associated with obesity whereas loss of weight is a feature of the disease; however, the two states are not mutually exclusive. Obesity is linked with changes in hormonal activity and overall body metabolism.

Materials and methods

In this study, 408 T2D patients were recruited in three distinct studies conducted in Bahrain, Saudi Arabia, and Kuwait in three different intervals between 2001 and 2019. In addition to demographics, glycemic and lipid profiles were obtained in all studies, whereas plasma insulin and HOMA-IR, vitamin D, and ghrelin were analyzed in Saudi Arabia. Different techniques such as chemical auto-analyzer, ELISA, chemiluminescent immunoassay, radioimmunoassay were used.

Results

The obese (BMI ≥ 30 kg/m2) compared with nonobese (BMI 18.5 to <30) patients with diabetes were more likely to be women (P < 0.001), smaller in age (P = 0.028), and with shorter disease duration (P = 0.018). Unexpectedly, the glycemic and lipid profiles were consistently comparable between the two groups in the three sites. Furthermore, vitamin D was strikingly lower in obese patients with diabetes (P = 0.007). Finally, plasma ghrelin (P = 0.163), insulin (P = 0.063), and HOMA-IR (P = 0.166) were comparable between obese and nonobese patients with diabetes.

Conclusion

Diabetic obesity was significantly associated with female sex, young age, short disease duration, and noticeably low vitamin D, and a trend of high insulin levels. However, the obese and nonobese patients had comparable metabolic profiles with no differences in insulin resistance and ghrelin levels. Further studies, especially at a molecular level, are needed to explore this topic which is barely investigated.
Rare genera differentiate urban green space soil bacterial communities in three cities across the world
Authors: Mills Jacob G. , Selway Caitlin A. , Weyrich Laura S. , Skelly Chris , Weinstein Philip , Thomas Torsten , Young Jennifer M. , Marczylo Emma , Yadav Sudesh , Yadav Vijay , Lowe Andrew J. , Breed Martin F.
Published: January 2022

Vegetation complexity is potentially important for urban green space designs aimed at fostering microbial biodiversity to benefit human health. Exposure to urban microbial biodiversity may influence human health outcomes via immune training and regulation. In this context, improving human exposure to microbiota via biodiversity-centric urban green space designs is an underused opportunity. There is currently little knowledge on the association between vegetation complexity (i.e. diversity and structure) and soil microbiota of urban green spaces. Here, we investigated the association between vegetation complexity and soil bacteria in urban green spaces in Bournemouth, UK; Haikou, China; and the City of Playford, Australia by sequencing the 16S rRNA V4 gene region of soil samples and assessing bacterial diversity. We characterized these green spaces as having ‘low’ or ‘high’ vegetation complexity and explored whether these two broad categories contained similar bacterial community compositions and diversity around the world. Within cities, we observed significantly different alpha and beta diversities between vegetation complexities; however, these results varied between cities. Rare genera (<1% relative abundance individually, on average 35% relative abundance when pooled) were most likely to be significantly different in sequence abundance between vegetation complexities and therefore explained much of the differences in microbial communities observed. Overall, general associations exist between soil bacterial communities and vegetation complexity, although these are not consistent between cities. Therefore, more in-depth work is required to be done locally to derive practical actions to assist the conservation and restoration of microbial communities in urban areas.
Caproicibacterium lactatifermentans sp. nov., isolated from pit clay used for the production of Chinese strong aroma-type liquor
Authors: Wang Huilin , Gu Yang , Zhao Dong , Qiao Zongwei , Zheng Jia , Gao Jiangjing , Ren Cong , Xu Yan
Published: January 2022

Two recently reported bacterial strains that were identified as the dominant caproate-producing bacteria in pit clay, were further characterized to determine their phylogeny and taxonomy. The two strains, designated as LBM19010T and JNU-WLY1368, were short rod-shaped, Gram-stain-positive, non-motile and strictly anaerobic. Analysis of the 16S rRNA gene sequences revealed that strains LBM19010T and JNU-WLY1368 shared a 16S rRNA gene sequence similarity of 99.93 % and belonged to a recent proposed genus

Caproicibacterium

in the family

Oscillospiraceae

. The proposed type strain, LBM19010T, showed the highest 16S rRNA gene sequence similarity to

Caproicibacterium amylolyticum

LBM18003T (96.34%), followed by

Caproiciproducens galactitolivorans

JCM 30532T (94.14 %). The pairwise average nucleotide identity and average amino acid identity values between strains LBM19010T and LBM18003T were 74.84 and 76.18 %, respectively. Growth of strain LBM19010T occurred at pH 4.5–7.5 (optimum, pH 5.0–5.5), 20–40 °C (optimum, 35 °C) and with 0–1 % (w/v) NaCl (optimum, 0 %). Strains LBM19010T and JNU-WLY1368 were both able to ferment several hexoses, disaccharides, starch and lactate but not pentoses. Caproate and butyrate were the major end-products from glucose. The predominant cellular fatty acids (>10 %) of strain LBM19010T were C16 : 0 (56.3 %), C14 : 0 DMA (19.5 %) and C14 : 0 (14.9 %). The identified polar lipids of strain LBM19010T were diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids and nine unidentified glycolipids. Based on phylogenetic, phenotypic and chemotaxonomic evidence, strains LBM19010T and JNU-WLY1368 belong to a novel species of the genus

Caproicibacterium

, for which the name Caproicibacterium lactatifermentans sp. nov. is proposed. The type strain is LBM19010T (=GDMCC 1.1627T=JCM 33782T).
Comparative diagnostic performance of the new chromatographic Affimer®-based rapid antigen detection against SARS-CoV-2 and other standard antigen tests for COVID-19 in a clinical setting
Authors: Gil-Garcia A.I. , Lopez-Lopez A. , Rubio J.M. , Montoya J.J. , Ouahid Y. , Madejon A. , Castan P.
Published: January 2022

The availability of accurate and rapid diagnostic tools for COVID-19 is essential for tackling the ongoing pandemic. In this context, researchers in the UK have started testing a new Lateral Flow Device (LFD) based on proprietary Biotinylated anti SARS-CoV-2 S1 Affimer® technology that binds to the SARS-CoV2-S1 protein in anterior nasal swab samples, generating an ultra-sensitive method for detection. This international study aimed to compare its performance against other available antigen-detecting rapid diagnostic tests (Ag-RDTs) in a real-world clinical setting. The study was completed under the frame of Project SENSORNAS RTC-20176501 in collaboration with MiRNAX Biosens Ltd. and Hospital Carlos III, it was documented internally and deposited in agreement to the ISO 13485 norm. All the data obtained are currently under submission and review from the Ethics Committee of Universidad Autonoma de Madrid.
Point-of-Care MRI with Artificial Intelligence to Measure Midline Shift in Acute Stroke Follow-Up
Authors: Kundu Prantik , Mohseni Salehi Seyed Sadegh , Cahn Bradley A. , Mazurek Mercy H. , Yuen Matthew M. , Welch E. Brian , Gordon-Kundu Barbara S. , Schlemper Jo , Sze Gordon , Kimberly W. Taylor , Rothberg Jonathan M. , Sofka Michal , Sheth Kevin N.
Published: January 2022

Background and Purpose

In stroke, timely treatment is vital for preserving neurologic function. However, decision-making in neurocritical care is hindered by limited accessibility of neuroimaging and radiological interpretation. We evaluated an artificial intelligence (AI) system for use in conjunction with bedside portable point-of-care (POC)-MRI to automatically measure midline shift (MLS), a quantitative biomarker of stroke severity.

Materials and Methods

POC-MRI (0.064 T) was acquired in a patient cohort (n=94) in the Neurosciences Intensive Care Unit (NICU) of an academic medical center in the follow-up window during treatment for ischemic stroke (IS) and hemorrhagic stroke (HS). A deep-learning architecture was applied to produce AI estimates of midline shift (MLS-AI). Neuroradiologist annotations for MLS were compared to MLS-AI using non-inferiority testing. Regression analysis was used to evaluate associations between MLS-AI and stroke severity (NIHSS) and functional disability (mRS) at imaging time and discharge, and the predictive value of MLS-AI versus clinical outcome was evaluated.

Results

MLS-AI was non-inferior to neuroradiologist estimates of MLS (p<1e-5). MLS-AI measurements were associated with stroke severity (NIHSS) near the time of imaging in all patients (p<0.005) and within the IS subgroup (p=0.005). In multivariate analysis, larger MLS-AI at the time of imaging was associated with significantly worse outcome at the time of discharge in all patients and in the IS subgroup (p<0.05). POC-MRI with MLS-AI >1.5 mm was positively predictive of poor discharge outcome in all patients (PPV=70%) and specifically in patients with IS (PPV=77%).

Conclusion

The integration of portable POC-MRI and AI provides automatic MLS measurements that were not inferior to time-consuming, manual measurements from expert neuroradiologists, potentially reducing neuroradiological burden for follow-up imaging in acute stroke.
Smart sealants for prevention and monitoring of gastrointestinal anastomotic leaks using portable smartphone-controlled ultrasound transducers
Authors: Anthis Alexandre H.C. , Abundo Maria Paulene , Neuer Anna L. , Tsolaki Elena , Rosendorf Jachym , Rduch Thomas , Starsich Fabian H.L. , Liska Vaclav , Schlegel Andrea A. , Shapiro Mikhail G. , Herrmann Inge K.
Published: January 2022

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of the cases. Penetration of digestive fluids into the peritoneal cavity may lead to dreadful complications, including sepsis and premature death. Modern suture supports and tissue adhesives only insufficiently address the issue. Due to the scarcity of alternatives, surgeons rely on monitoring surrogate markers and clinical symptoms, which oftentimes lack sensitivity and specificity, hence only offering late-stage detection of already fully developed leaks.

Here, a first-of-its-kind, modular, intelligent suture support patch capable of sealing and monitoring leaks under harsh gastrointestinal conditions is presented. The smart adhesive layered hydrogel patch provides, in addition to unprecedented tissue sealing under most demanding conditions, unique leak-detection capabilities based on pH and/or enzyme-responsive sensing elements, which can be read out by non-invasive point-of-need ultrasound imaging. Reliable detection of the breaching of sutures in as little as 3 hours in intestinal leak and 15 minutes in gastric leak conditions, and before an actual leak develops, is demonstrated. This technology paves the way for next-generation suture support materials that offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.

Electronic-free smart surgical hydrogel sealants leveraging tissue-penetrating polymer networks and trigger-responsive echogenic entities to enable point-of-need monitoring and early anastomotic leak detection using a hand-held ultrasound transducer and a smartphone.
A cellular hierarchy framework for understanding heterogeneity and predicting drug response in AML
Authors: Zeng Andy G.X. , Bansal Suraj , Jin Liqing , Mitchell Amanda , Chen Weihsu Claire , Abbas Hussein A. , Chan-Seng-Yue Michelle , Voisin Veronique , van Galen Peter , Tierens Anne , Cheok Meyling , Preudhomme Claude , Dombret Hervé , Daver Naval , Futreal P Andrew , Minden Mark D. , Kennedy James A. , Wang Jean C.Y. , Dick John E.
Published: January 2022

The treatment landscape of AML is evolving with promising therapies entering clinical translation, yet patient responses remain heterogeneous and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy make-up from bulk transcriptomes of over 1000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor, and mature cell types. Leukemia hierarchy composition was associated with functional, genomic, and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP, and Intermediate. Critically, variation in hierarchy composition along the Primitive vs GMP or Primitive vs Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A 7-gene biomarker derived from the Primitive vs Mature axis was predictive of patient response to 105 investigational drugs. Thus, hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.
Establishment and characterization of novel autologous pair primary cultures from two Indian non-habitual tongue carcinoma patients
Authors: Dwivedi Nehanjali , Charitha G , Pillai Vijay , Kuriakose Moni A , Suresh Amritha , Das Manjula
Published: January 2022

Oral tongue squamous cell carcinoma (OTSCC) is one of the major causes of fatality in India owing to very high percentages of patients with smoking and chewing habits. Being highly heterogeneous in nature, every patient poses a different challenge clinically. To better understand disease progression, knowledge of cross talk between tumor stroma and the tumor cells becomes indispensable. Patient-derived in vitro cell line models are helpful to understand the complexity of diseases. However, they have very low efficiency of establishment from the tumor samples, especially the cancer associated fibroblasts (CAFs). In the present study, two novel autologous pairs have been immortalized spontaneously from non-habitual, HPV-positive patients, presented with tongue squamous cell carcinoma. The epithelial and fibroblast primary lines had typical polygonal and spindle shaped morphology, respectively. Positive staining with Pan-cytokeratin (PanCK) and Fibroblast Specific Protein (FSP-1) further confirmed their epithelial and fibroblast origin. Unique Short Tandem Repeat (STR) profile of the cultures confirmed their novelty, while the similarity of the STR profiles between the epithelial and fibroblast cells from the same patient, confirmed their autologous nature. DNA analysis revealed aneuploidy of the established cultures. Increase in the tumorigenic potential of the established epithelial cultures upon treatment with CAF-conditioned medium proved the “CAF-ness” of the established fibroblast cells. The established cultures are the first of their kind which would serve as an useful platform in understanding the cross talk between tumor-stroma and tumor, along with studying tongue cancer progression.
Needler: An Algorithm to Develop a Comprehensive Targeted MS Method Capable of Monitoring the Human Proteome
Authors: Ready Damien B. , Potts Gregory K.
Published: January 2022

Targeted proteomics for addressing biological hypotheses through quantitative mass spectrometry (MS) is increasingly popular because of its ability to deliver sensitive and reproducible results to inform protein concentration and dynamics. While the technique is powerful, the associated tooling to develop unique targeted data acquisition methods per experiment is limited, often focused on producing a minimally viable analytical approach for a limited set of analytes, rather than one which can maximally quantitate all targets of interest. We developed the Needler algorithm to produce comprehensive targeted MS methods capable of quantitating the maximum number of proteins given available instrument constraints. Using this algorithm, we demonstrate that the minimum instrument parameters required to produced targeted MS quantitation of all tryptic peptides from the human proteome are well in excess of current capabilities. Given these constraints, we provide a visualized scope of the boundaries for practical MS monitoring to maximize proteome and subproteome coverage dependent upon instrument duty cycle capabilities.
A computational method for predicting the most likely evolutionary trajectories in the step-wise accumulation of resistance mutations
Authors: Eccleston R. Charlotte , Manko Emilia , Campino Susana , Clark Taane G. , Furnham Nicholas
Published: January 2022

Pathogen evolution of drug resistance often occurs in a stepwise manner via the accumulation of multiple mutations that in combination have a non-additive impact on fitness, a phenomenon known as epistasis. The evolution of resistance via the accumulation of point mutations in the DHFR genes ofPlasmodium falciparum(Pf) andPlasmodium vivax(Pv) has been studied extensively and multiple studies have shown epistatic interactions between these mutations determine the accessible evolutionary trajectories to highly resistant multiple mutations. Here, we simulated these evolutionary trajectories using a model of molecular evolution, parameterized using Rosetta Flex ddG predictions, where selection acts to reduce the target-drug binding affinity. We observe strong agreement with pathways determined using experimentally measured IC50 values of pyrimethamine binding, which suggests binding affinity is strongly predictive of resistance and epistasis in binding affinity strongly influences the order of fixation of resistance mutations. We also infer pathways directly from the frequency of mutations found in isolate data, and observe remarkable agreement with the most likely pathways predicted by our mechanistic model, as well as those determined experimentally. This suggests mutation frequency data can be used to intuitively infer evolutionary pathways, provided sufficient sampling of the population.
PIMT suppresses endothelial activation and vascular inflammation through methylation of TRAF6
Authors: Zhang Chen , Guo Zhi-Fu , Yi Bing , Kazama Kyosuke , Liu Wennan , Sun Xiaobo , Wang Lu , Yang Xiao-Feng , Summer Ross , Sun Jianxin
Published: January 2022

As a repair enzyme, protein L-isoaspartyl O-methyltransferase (PIMT) methylates and converts isoaspartyl residues (isoAsp) back to conventional forms to avoid protein damage during aging and stress responses. This study aims to investigate the pathological significance of PIMT in vascular inflammation. Herein, we show that PIMT is highly expressed in lung endothelial cells (ECs), and its reduction significantly exacerbates pulmonary inflammation in a murine model of acute lung injury (ALI). Mechanistically, we identify tumor necrosis factor receptor-associated factor 6 (TRAF6) as a substrate of PIMT. PIMT-mediated methylation of TRAF6 inhibits TRAF6 oligomerization, autoubiquitination, and LPS-induced NF-κB transactivation in ECs. Importantly, in addition to transcriptionally attenuating expression of adhesion molecules, PIMT post-translationally impedes site specific N-glycosylation of intercellular adhesion molecule-1 (ICAM-1), which leads to an increased protein degradation of ICAM-1 and a subsequent inhibition of EC interaction with immune cells during inflammatory process. Our results for the first time identify PIMT-mediated protein O-methylation as a key post-translational mechanism in controlling vascular inflammation, and suggest that PIMT may represent a novel therapeutic target in inflammatory vascular diseases.
Despite the odds: formation of the SARS-CoV-2 methylation complex
Authors: Matsuda Alex , Plewka Jacek , Chykunova Yuliya , Jones Alisha N. , Pachota Magdalena , Rawski Michał , Mourão André , Karim Abdulkarim , Kresik Leanid , Lis Kinga , Minia Igor , Hartman Kinga , Sonani Ravi , Dubin Grzegorz , Sattler Michael , Suder Piotr , Mak Paweł , Popowicz Grzegorz M. , Pyrć Krzysztof , Czarna Anna
Published: January 2022

Coronaviruses protect their single-stranded RNA genome with a methylated cap during replication. The capping process is initiated by several nonstructural proteins (nsp) encoded in the viral genome. The methylation is performed by two methyltransferases, nsp14 and nsp16 where nsp10 acts as a co-factor to both. Aditionally, nsp14 carries an exonuclease domain, which operates in the proofreading system during RNA replication of the viral genome. Both nsp14 and nsp16 were reported to independently bind nsp10, but the available structural information suggests that the concomitant interaction between these three proteins should be impossible due to steric clashes. Here, we show that nsp14, nsp10, and nsp16 can form a heterotrimer complex. This interaction is expected to encourage formation of mature capped viral mRNA, modulating the nsp14’s exonuclease activity, and protecting the viral RNA. Our findings show that nsp14 is amenable to allosteric regulation and may serve as a novel target for therapeutic approaches.
Binocular visual experience and sleep promote visual cortex plasticity and restore binocular vision in a mouse model of amblyopia
Authors: Martinez Jessy D. , Donnelly Marcus J. , Popke Donald S. , Torres Daniel , Wilson Lydia G. , Brancaleone William P. , Clawson Brittany C. , Jiang Sha , Aton Sara J.
Published: January 2022

Amblyopia arises from an altered balance of input from the two eyes to the binocular zone of primary visual cortex (bV1) during childhood, causing long-lasting visual impairment. Amblyopia is commonly treated by patching the dominant eye, however, the relative impacts of monocular vs. binocular visual experiences on restoration of bV1 function remains unclear. Moreover, while sleep has been implicated in V1 plasticity in response to vision loss, its role in recovery from amblyopia is unknown. We used monocular deprivation (MD) in juvenile mice to model amblyopia in bV1. We compared recovery of visual responses for the two eyes among bV1 regular spiking (RS, putative principal) neurons and fast-spiking (FS, putative parvalbumin-expressing [PV+]) interneurons after identical-duration, identical-quality binocular recovery (BR) or monocular, reverse occlusion (RO) experiences. We find that BR is quantitatively superior to RO with respect to renormalizing both bV1 populations’ visual responses. However, this recovery was seen only in freely-sleeping mice; post-BR sleep deprivation prevented functional recovery. Thus, both binocular visual experience and subsequent sleep are required to optimally renormalize bV1 responses in a mouse model of amblyopia.