bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the interaction of 14-3-3 proteins with hDMX and hDM2: a structural and biophysical study
Authors: Srdanovic Sonja , Wolter Madita , Trinh Chi H. , Ottmann Christian , Warriner Stuart L. , Wilson Andrew J.
Published: December 2021

p53 plays a critical role in regulating diverse biological processes: DNA repair, cell cycle arrest, apoptosis, and senescence. The p53 pathway has therefore served as the focus for drug-discovery efforts. p53 is negatively regulated by hDMX and hDM2; prior studies have identified 14-3-3 proteins as hDMX and hDM2 client proteins. 14-3-3 proteins are adaptor proteins that modulate localisation, degradation and interactions of their targets in response to phosphorylation. Thus 14-3-3 proteins may indirectly modulate the interaction between hDMX or hDM2 and p53 and represent potential targets for modulation of the p53 pathway. In this manuscript we report on the biophysical and structural characterization of peptide/protein interactions that are representative of the interaction between 14-3-3 and hDMX or hDM2. The data establish that proximal phosphosites spaced ∼20-25 residues apart in both hDMX and hDM2 co-operate to facilitate high-affinity 14-3-3 binding and provide structural insight that can be utilized in future stabilizer/inhibitor discovery efforts.
Structural basis for the assembly and electron transport mechanisms of the dimeric photosynthetic RC–LH1 supercomplex
Authors: Cao Peng , Bracun Laura , Yamagata Atsushi , Christianson Bern M. , Negami Tatsuki , Zou Baohua , Terada Tohru , Canniffe Daniel P. , Shirouzu Mikako , Li Mei , Liu Lu-Ning
Published: December 2021

The reaction center (RC) and light-harvesting complex 1 (LH1) form a RC–LH1 core supercomplex that is vital for the primary reactions of photosynthesis in purple photosynthetic bacteria. Some species possess the dimeric RC–LH1 complex with an additional polypeptide PufX, representing the largest photosynthetic complex in anoxygenic phototrophs. However, the details of the architecture and assembly mechanism of the RC–LH1 dimer are unclear. Here we report seven cryo-electron microscopy (cryo-EM) structures of RC–LH1 supercomplexes from Rhodobacter sphaeroides. Our structures reveal that two PufX polypeptides are positioned in the center of the S-shaped RC–LH1 dimer, interlocking association between the components and mediating RC–LH1 dimerization. Moreover, we identify a new transmembrane peptide, designated PufY, which is located between the RC and LH1 subunits near the LH1 opening. PufY binds a quinone molecule and prevents LH1 subunits from completely encircling the RC, creating a channel for quinone/quinol exchange. Genetic mutagenesis, cryo-EM structures, and computational simulations enable a mechanistic understanding of the assembly and electron transport pathways of the RC–LH1 dimer and elucidate the roles of individual components in ensuring the structural and functional integrity of the photosynthetic supercomplex.
Mechanisms underlying sequence-dependent DNA hybridisation rates in the absence of secondary structure
Authors: Hertel Sophie , Spinney Richard E. , Xu Stephanie Y. , Ouldridge Thomas E. , Morris Richard G. , Lee Lawrence K.
Published: December 2021

The kinetics of DNA hybridisation are fundamental to biological processes and DNA-based technologies. However, the precise physical mechanisms that determine why different DNA sequences hybridise at different rates are not well understood. Secondary structure is one predictable factor that influences hybridisation rates but is not sufficient on its own to fully explain the observed sequence-dependent variance. Consequently, to achieve a good correlation with experimental data, current prediction algorithms require many parameters that provide little mechanistic insight into DNA hybridisation. In this context, we measured hybridisation rates of 43 different DNA sequences that are not predicted to form secondary structure and present a parsimonious physically justified model to quantify their hybridisation rates. Accounting only for the combinatorics of complementary nucleating interactions and their sequence-dependent stability, the model achieves good correlation with experiment with only two free parameters, thus providing new insight into the physical factors underpinning DNA hybridisation rates.
KDM6B sensitizes PARthanatos via suppression of O6-methylguanine DNA methyltransferase repair and sustained checkpoint response
Authors: Yang Mingming , Wang Chenliang , Zhou Mi , Bao Lei , Wang Yanan , Kumar Ashwani , Xing Chao , Luo Weibo , Wang Yingfei
Published: December 2021

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA damage sensor and contributes to both DNA repair and cell death processes. However, how PARP-1 signaling is regulated to switch its function from DNA repair to cell death remains largely unknown. Here, we found that PARP-1 plays a central role in alkylating agent-induced PARthanatic cancer cell death. Lysine demethylase 6B (KDM6B) was identified as a key cell death effector in PARthanatos. Knockout of KDM6B or loss of KDM6B demethylase activity conferred cancer cells resistance to PARthanatic cell death in response to alkylating agents. Mechanistically, KDM6B knockout suppressed methylation at the promoter of O6-methylguanine-DNA methyltransferase (MGMT) to enhance MGMT expression and its direct DNA repair function, thereby inhibiting DNA damage-evoked PARP-1 hyperactivation and subsequent cell death. Moreover, KDM6B knockout triggered sustained Chk1 phosphorylation and activated a second repair machinery to fix DNA damage evading from MGMT repair. Inhibition of MGMT or checkpoint response re-sensitized KDM6B deficient cells to PARthanatos induced by alkylating agents. These findings provide new molecular insights into epigenetic regulation of PARP-1 signaling mediating DNA repair or cell death and identify KDM6B as a biomarker for prediction of cancer cell vulnerability to alkylating agent treatment.
Dynamic localisation of DamX regulates bacterial filamentation and division during UPEC dispersal from host cells
Authors: Söderström Bill , Daley Daniel O. , Duggin Iain G.
Published: December 2021

Uropathogenic Escherichia coli (UPEC) cells can grow into highly filamentous forms during infection of bladder epithelial cells, but this process is poorly understood. Herein we found that some UPEC filaments released from infected bladder cells in vitro grew very rapidly and by more than 100 µm before initiating division, whereas others did not survive, suggesting that filamentation is a stress response that promotes dispersal. The DamX bifunctional division protein, which is essential for UPEC filamentation, was initially non-localized but then assembled at multiple division sites in the filaments prior to division. DamX rings maintained consistent thickness during constriction and remained at the septum until after membrane fusion was completed, like in rod cell division. Our findings suggest a mechanism involving regulated dissipation of DamX, leading to division arrest and filamentation, followed by its reassembly into division rings to promote UPEC dispersal and survival during infection.
Escherichia coli BarA-UvrY regulates the pks island and kills Staphylococci via the genotoxin colibactin
Authors: Wong Jun Jie , Chong Kelvin K.L. , Ho Foo Kiong , Benjamin Ho Chee Meng , Neelakandan Ramesh , Choo Pei Yi , Keogh Damien , Chen John , Liu Chuan Fa , Kline Kimberly A.
Published: December 2021

Wound infections are often polymicrobial in nature and are associated with poor disease prognoses. Escherichia coli and Staphylococcus aureus are among the top five most cultured pathogens from wound infections. However, little is known about the polymicrobial interactions between E. coli and S. aureus during wound infections. In this study, we show that E. coli kills S. aureus both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. We also show that the BarA-UvrY two component system (TCS) is a novel regulator of the pks island, which acts through the carbon storage global regulatory (Csr) system. Together, our data demonstrate the role of colibactin in inter-species competition and show that it is regulated by BarA-UvrY TCS, a previously uncharacterized regulator of the pks island.
COVID-19 endgame: from pandemic to endemic? Vaccination, reopening and evolution in a well-vaccinated population
Authors: Are Elisha B. , Song Yexuan , Stockdale Jessica E. , Tupper Paul , Colijn Caroline
Published: December 2021

COVID-19 remains a major public health concern, with large resurgences even where there has been widespread uptake of vaccines. Waning immunity and the emergence of new variants will shape the long-term burden and dynamics of COVID-19. We explore the transition to the endemic state, and the endemic incidence, using a combination of modelling approaches. We compare gradual and rapid reopening and reopening at different vaccination levels. We examine how the eventual endemic state depends on the duration of immunity, the rate of importations, the efficacy of vaccines and the transmissibility. These depend on the evolution of the virus, which continues to undergo selection. Slower reopening leads to a lower peak level of incidence and fewer overall infections: as much as a 60% lower peak and a 10% lower total in some illustrative simulations; under realistic parameters, reopening when 70% of the population is vaccinated leads to a large resurgence in cases. The long-term endemic behaviour may stabilize as late as January 2023, with further waves of high incidence occurring depending on the transmissibility of the prevalent variant, duration of immunity, and antigenic drift. We find that long term endemic levels are not necessarily lower than current pandemic levels: in a population of 100,000 with representative parameter settings (Reproduction number 5, 1-year duration of immunity, vaccine efficacy at 80% and importations at 3 cases per 100K per day) there are over 100 daily incident cases in the model. The consequent burden on health care systems depends on the severity of infection in immunized or previously infected individuals.
Evaluation of the Implementation of the 4C Mortality Score in United Kingdom hospitals during the second pandemic wave
Authors: Blunsum Andrew E. , Perkins Jonathan S. , Arshad Areeb , Bajpai Sukrit , Barclay-Elliott Karen , Brito-Mutunayagam Sanjita , Brooks Rebecca , Chan Terrence , Coates Dominic J. G. , Corobana Alina , Crocker-Buqué Tim , Evans Terry J. , Gordon-Brown Jasmine , Hack Berkin , Hiles Heather , Khanijau Aakash , Lalwani Salina , Leong Clare , MacKay Kirsty , Macrae Catriona , Martin Bryony , Martin Christopher A. , McKemey Emily , Nazareth Joshua , Pan Daniel , Scopazzini Marcello , Simons David , Swinhoe Sophie , Thomas Julia , Thorburn Fiona , Walpole Sarah , Warne Esmie , Wilson Rory , MacConnachie Alisdair , Ho Antonia
Published: December 2021

The 4C Mortality Score (4C Score) was designed to risk stratify hospitalised patients with COVID-19. We assessed inclusion of 4C Score in COVID-19 management guidance and its documentation in patients’ case notes in January 2021 in UK hospitals. 4C Score was included within guidance by 50% of sites, though score documentation in case notes was highly variable. Higher documentation of 4C Score was associated with score integration within admissions proformas, inclusion of 4C Score variables or link to online calculator, and management decisions. Integration of 4C Score within clinical pathways may encourage more widespread use.
Measurement of the extent of Anxiety and Depression that has occurred in college students due to the COVID 19 pandemic: A Survey based cross-secConal study
Authors: Goswami Shubham , Chakraborty Soujanya , Chakraborty Aritra
Published: December 2021

OVERVIEW

The ongoing Pandemic because of the Coronavirus disease 2019 (COVID-19) has caused all the educational institutes including colleges to be closed for a very long time. As a result the students are compelled to remain in their homes for this time. Prolonged stay at home along with excess use of social media and other modes to “kill” the time are quite famous to cause certain health issues in a person, specially the teenagers and adolescents. Mental wellbegin, being a dimension of health as per WHO should not be ignored at all specially in these situations.

METHOD OF STUDY

An Online Questionnaire is prepared based of the ZUNG Self Rating Anxiety and Self Rating Depression Scale (Pre-validated Scales). The Form is circulated digitally among the people and then we have collected the data in excel. Based on the result we have prepared our statistical chart.

RESULT

Quite a significant number of candidates were suffering due to the pandemic situation. 17.091% were suffering from mild to moderate anxiety, 1.785% had marked to severe anxiety levels(Constituting approximately 18.9% of the total). On the other hand, 8.673% of the students had mild depression, while 1 candidate (0.255%) had moderate depression and 1 (0.255%) had severe depression, (Constituting approximately 9.20% of the total). We found that candidates in the age group of 23-24 years had the maximum prevalence of depression, it was followed by candidates with age between 21-22 years. We found that the candidates with age between 23 to 24 years were having highest prevalence of significant anxiety levels which is closely followed by candidates having age which lies between 22 years to 23 years.
SARS-CoV-2 transmission potential and rural-urban disease burden disparities across Alabama, Louisiana, and Mississippi, March 2020 — May 2021
Authors: Ofori Sylvia K. , Ogwara Chigozie A. , Kwon Seoyon , Hua Xinyi , Martin Kamryn M. , Mallhi Arshpreet Kaur , Twum Felix , Chowell Gerardo , Fung Isaac C.-H.
Published: December 2021

Purpose

To quantify and compare SARS-CoV-2 transmission potential across Alabama, Louisiana, and Mississippi and selected counties with populations in the 50th, 75th, and 100th percentile.

Methods

To determine the time-varying reproduction number Rt of SARS-CoV-2, we applied the R package EpiEstim to the time series of daily incidence of confirmed cases. Median Rt percentage change when policies changed was determined. Linear regression was performed between log10-transformed cumulative incidence and log10-transformed population size at four time points.

Results

Stay-at-home orders, face mask mandates, and vaccinations were associated with the most significant reductions in SARS-CoV-2 transmission in the three southern states. Rt across the three states decreased significantly by 20% following stay-at-home orders. We observed varying degrees of reductions in Rt across states following other policies. Rural Alabama counties experienced higher per capita cumulative cases relative to urban ones as of June 17 and October 17, 2020. Meanwhile, Louisiana and Mississippi saw the disproportionate impact of SARS-CoV-2 in rural counties compared to urban ones throughout the study period.

Conclusion

State and county policies had an impact on local pandemic trajectories. The rural-urban disparities in case burden call for evidence-based approaches in tailoring health promotion interventions and vaccination campaigns to rural residents.
Differential auditory and visual phase-locking are observed during audio-visual benefit and silent lip-reading for speech perception
Authors: Aller Máté , Økland Heidi Solberg , MacGregor Lucy J. , Blank Helen , Davis Matthew H.
Published: December 2021

Speech perception in noisy environments is enhanced by seeing facial movements of communication partners. However, the neural mechanisms by which audio and visual speech are combined are not fully understood. We explore MEG phase locking to auditory and visual signals in MEG recordings from 14 human participants (6 females, 8 males) that reported words from single spoken sentences. We manipulated the acoustic clarity and visual speech signals such that critical speech information is present in auditory, visual or both modalities. MEG coherence analysis revealed that both auditory and visual speech envelopes (auditory amplitude modulations and lip aperture changes) were phase-locked to 2-6Hz brain responses in auditory and visual cortex, consistent with entrainment to syllable-rate components. Partial coherence analysis was used to separate neural responses to correlated audio-visual signals and showed non-zero phase locking to auditory envelope in occipital cortex during audio-visual (AV) speech. Furthermore, phase-locking to auditory signals in visual cortex was enhanced for AV speech compared to audio-only (AO) speech that was matched for intelligibility. Conversely, auditory regions of the superior temporal gyrus (STG) did not show above-chance partial coherence with visual speech signals during AV conditions, but did show partial coherence in VO conditions. Hence, visual speech enabled stronger phase locking to auditory signals in visual areas, whereas phase-locking of visual speech in auditory regions only occurred during silent lip-reading. Differences in these cross-modal interactions between auditory and visual speech signals are interpreted in line with cross-modal predictive mechanisms during speech perception.

Significance Statement

Verbal communication in noisy environments is challenging, especially for hearing-impaired individuals. Seeing facial movements of communication partners improves speech perception when auditory signals are degraded or absent. The neural mechanisms supporting lip-reading or audio-visual benefit are not fully understood. Using MEG recordings and partial coherence analysis we show that speech information is used differently in brain regions that respond to auditory and visual speech. While visual areas use visual speech to improve phase-locking to auditory speech signals, auditory areas do not show phase-locking to visual speech unless auditory speech is absent and visual speech is used to substitute for missing auditory signals. These findings highlight brain processes that combine visual and auditory signals to support speech understanding.
Epithelial cells of the intestine acquire cell-intrinsic inflammation signatures during ageing
Authors: Funk Maja C. , Gleixner Jan G. , Heigwer Florian , Valentini Erica , Aydin Zeynep , Tonin Elena , Hetzer Jenny , Heide Danijela , Stegle Oliver , Heikenwalder Mathias , Boutros Michael
Published: December 2021

During ageing, cell-intrinsic and extrinsic factors lead to the decline of tissue function and organismal health. Disentangling these factors is important for developing effective strategies to prolong organismal healthspan. Here, we addressed this question in the mouse intestinal epithelium, which forms a dynamic interface with its microenvironment and receives extrinsic signals affecting its homeostasis and tissue ageing. We systematically compared transcriptional profiles of young and aged epithelial cells in vivo and ex vivo in cultured intestinal organoids. We found that all cell types of the aged epithelium exhibit an inflammation phenotype, which is marked by MHC class II upregulation and most pronounced in enterocytes. This was accompanied by elevated levels of the immune tolerance markers PD-1 and PD-L1 in the aged tissue microenvironment, indicating dysregulation of immunological homeostasis. Intestinal organoids from aged mice still showed an inflammation signature after weeks in culture, which was concurrent with increased chromatin accessibility of inflammation-associated loci. Our results reveal a cell-intrinsic, persistent inflammation phenotype in aged epithelial cells, which might contribute to systemic inflammation observed during ageing.
Insitu tubularisation of skin graft for re‐do hypospadias repairment
Authors: Atan Ali , Turkyilmaz Zafer , Karabulut Ramazan , Kaya Cem , Polat Fazli , Sonmez Kaan
Published: December 2021

We describe in situ skin graft tubularisation over the urethral catheter. This tehnique allows preparation of a urethral tube on a fixed line and suture the wound sides comfortably while preventing the movement of the graft.
Primary hepatic mucosa‐associated lymphoid tissue lymphoma: Case report and literature review
Authors: Lau Wing Yu , Ho Kit‐Man , Chan Fiona Ka‐Man , Lam Shi , Cheng Kai‐Chi
Published: December 2021

Primary hepatic mucosa‐associated lymphoid tissue lymphoma (MALToma) is a very rare disease and the diagnosis is often only made after histologic examination. To date, there is no consensus on its treatment modalities. In this paper, we report a case of primary hepatic MALToma and literature review of this rare disease. Our patient was a 72‐year‐old woman who presented with elevated alkaline phosphatase level. She was neither a hepatitis B nor C carrier. The alpha‐fetoprotein level was normal. Ultrasound of the abdomen found two hypoechoic liver lesions. Triphasic contrast computed tomography of the liver showed two arterial enhancing lesions with portovenous and delayed washout at segment 2 (1.7 cm) and segment 4b (2.5 cm), respectively. Fluorodeoxyglucose‐positron emission tomography showed two hypermetabolic foci in segments 2 and 4b of the liver, respectively, compatible with hepatocellular carcinoma. There was diffuse fluorodeoxyglucose uptake in the stomach. Oesophagogastroduodenoscopy (OGD) was performed, which showed diffuse gastritis only. Laparoscopic left hepatectomy was performed for the suspected hepatocellular carcinoma. Histological examination demonstrated the diagnosis of MALToma. Further bone marrow trephine did not show any bone marrow involvement by the lymphoma. The patient refused adjuvant chemotherapy.
An interview study to identify circulating nurses’ nontechnical skills
Authors: Kalantari Reza , Zamanian Zahra , Hasanshahi Mehdi , Faghihi Seyed Ali Akbar , Niakan Mohammad Hadi , Jamali Jamshid , Gheysari Somayeh
Published: December 2021

Aim

Non‐technical skills are component features of human factors whose defects can lead to surgical errors and adverse events. Circulating nurses need to deploy non‐technical skills for safe and efficient performance. This study aimed to identify circulating nurses’ non‐technical skills.

Methods

This interview study was conducted on 29 operating room personnel. Semi‐structured interviews were used for data collection. The prepared annotated transcripts were analysed using the content analysis method by a human factors specialist under the supervision of two other researchers. The extracted behaviours were grouped based on meaning and similarity.

Results

Six categories of non‐technical skills including leadership, communication, task management, situational awareness, teamwork, and coping were identified as the circulating nurses’ key non‐technical skills. The related behaviours were also noted.

Conclusion

Non‐technical skills are incorporated in circulating nurses’ tasks from the onset to the end of surgery. Thus, these nurses should be aware of the necessary non‐technical skills and positive behaviours to assure a safe surgery.
Executive Deferral Plans and Insider Trading†
Authors: Franco Francesca , Urcan Oktay
Published: December 2021

We study executive equity contributions to nonqualified deferred compensation plans, which consist of the election to defer part or all of the executive's annual base salary and other cash pay into the company's stock. These transactions provide executives with an alternative channel to purchase shares in the firm while benefiting from an affirmative defense against illegal insider‐trading allegations. Using a large sample of executive equity deferrals over 2000–2014, we find evidence that executives use these transactions as a means to acquire the company's stock during blackout windows. Consistent with the conjecture that deferrals can benefit from lower litigation costs that inhibit insider trades before the release of corporate news, we also find that the deferred amounts are significantly higher (lower) before the disclosure of good (bad) earnings news. These results suggest that executives can use equity deferrals to circumvent Rule 10b5 trading restrictions and generate significant returns through the timing and content of corporate disclosures around these transactions. Together, our evidence supports the recent concerns that executives might be engaging in strategic information releases around Rule 10b5 transactions.
Genetic and environmental influences on the progression from alcohol use disorder to alcohol‐related medical conditions
Authors: Edwards Alexis C. , Sundquist Kristina , Sundquist Jan , Kendler Kenneth S. , Larsson Lönn Sara
Published: December 2021

Background

Medical conditions related to alcohol use disorders (AUD) represent a substantial public health concern. However, only a subset of individuals with AUD develop these conditions and the extent to which genetic and environmental factors that are shared with AUD, versus those distinct from it, contribute to this progression has not yet been determined.

Methods

Using data from Swedish national registries for a cohort born from 1932 to 1970 (N = 1,319,214, 48.9% women), we conducted twin‐sibling biometric model fitting to examine the genetic and environmental sources of variance that contribute to the liability to alcohol‐related medical conditions (AMC). Progression to AMC, determined using medical registry data, was contingent on an AUD registration, which was determined using medical and criminal registry data.

Results

We identified AUD registrations in 3.2% of women and 9.2% of men. Among individuals with an AUD registration, 14.4% of women and 15.4% of men had an AMC registration. In the final models, we constrained the beta pathway from AUD to AMC and the genetic and unique environmental paths to be equal across sexes. The beta path was estimated at 0.59. AMC was modestly heritable in women (A = 0.32) and men (A = 0.30). The proportion of total heritability unique to AMC was 39.6% among women and 41.3% among men. A higher proportion of total environmental variance was unique to AMC: 76.7% for women and 77.2% for men. In a sensitivity analysis limited to liver‐related AMC, we observed similar results, with a slightly lower beta path from AUD to AMC (0.46) and higher proportions of AMC‐specific genetic (70.0% in women; 71.7% in men) and environmental (84.5% in both sexes) variance.

Conclusions

A moderate‐to‐substantial proportion of genetic and environmental variance that contributes to AMC risk is not shared with AUD, underscoring the need for additional gene identification efforts for AMC. Furthermore, the prominent influence of environmental factors specific to AMC provides a promising area for the identification of prevention targets. We did not observe significant sex differences in the etiology of AMC, although follow‐up is warranted in other well‐powered studies.
Discriminating between patients with unipolar disorder, bipolar disorder, and healthy control individuals based on voice features collected from naturalistic smartphone calls
Authors: Faurholt‐Jepsen Maria , Rohani Darius Adam , Busk Jonas , Tønning Morten Lindberg , Vinberg Maj , Bardram Jakob Eyvind , Kessing Lars Vedel
Published: December 2021

Background

It is of crucial importance to be able to discriminate unipolar disorder (UD) from bipolar disorder (BD), as treatments, as well as course of illness, differ between the two disorders. Aims: To investigate whether voice features from naturalistic phone calls could discriminate between (1) UD, BD, and healthy control individuals (HC); (2) different states within UD.

Methods

Voice features were collected daily during naturalistic phone calls for up to 972 days. A total of 48 patients with UD, 121 patients with BD, and 38 HC were included. A total of 115,483 voice data entries were collected (UD [n = 16,454], BD [n = 78,733], and HC [n = 20,296]). Patients evaluated symptoms daily using a smartphone‐based system, making it possible to define illness states within UD and BD. Data were analyzed using random forest algorithms.

Results

Compared with BD, UD was classified with a specificity of 0.84 (SD: 0.07)/AUC of 0.58 (SD: 0.07) and compared with HC with a sensitivity of 0.74 (SD: 0.10)/AUC = 0.74 (SD: 0.06). Compared with BD during euthymia, UD during euthymia was classified with a specificity of 0.79 (SD: 0.05)/AUC = 0.43 (SD: 0.16).

Compared with BD during depression, UD during depression was classified with a specificity of 0.81 (SD: 0.09)/AUC = 0.48 (SD: 0.12). Within UD, compared with euthymia, depression was classified with a specificity of 0.70 (SD 0.31)/AUC = 0.65 (SD: 0.11). In all models, the user‐dependent models outperformed the user‐independent models.

Conclusions

The results from the present study are promising, but as reflected by the low AUCs, does not support that voice features collected during naturalistic phone calls at the current state of art can be implemented in clinical practice as a supplementary and assisting tool. Further studies are needed.
Management of primary spontaneous pneumothorax in teenagers: An 11‐year study
Authors: Benhaïm Eve , Roth Brimbelle , Michel Fabrice , Merrot Thierry , Dubus Jean‐Christophe
Published: December 2021

Aim

Management of teenagers with primary spontaneous pneumothorax (PSP) is not consensual. We report our experience over an 11‐year period.

Methods

For each patient under 20 years hospitalised with PSP from 2008 to 2018, demographic data, smoking habits, clinical presentation, hospitalisation unit, radiological management and its results, therapeutic management (observation, needle aspiration, chest tube drainage and surgery), complications, length of stay, given advice at discharge and recurrence were collected.

Results

Seventy patients were included in different paediatric or adult surgery or pulmonology wards (82.9% boys; 16.8 ± 1.7 years; one severe presentation; 18/58 smokers). Chest CT‐scan (n = 42/70, 60%) revealed blebs/bullae in 18/39 examinations (46.2%). Treatment consisted of observation (14/70, 20%), needle aspiration (2/70, 2.9%), chest tube (53/70, 75.7%) and video‐assisted thoracoscopy surgery (27/70, 38.6%). Half patients with interventional procedure presented complications. A median of 10 chest X‐rays was noted during a median stay of 8 days. Advice concerning sport practice, flying, smoking, etc., was variably delivered. PSP recurrence concerned 35/70 patients (50%) without identified predictive factors.

Conclusion

Compared to recent recommendations of a more conservative approach, chest CT‐scan and interventional strategy are overused in our teenagers with PSP. Observation, more or less needle aspiration, should be clearly the first‐line treatments.
Diagnosis and treatment of chronic synovitis in patients with haemophilia: consensus statements from the Italian Association of Haemophilia Centres
Authors: Di Minno Matteo Nicola Dario , Napolitano Mariasanta , Giuffrida Anna Chiara , Baldacci Erminia , Carulli Christian , Boccalandro Elena , Bruno Clarissa , Forneris Eleonora , Ricca Irene , Passeri Walter , Martinelli Marco , Rivolta Gianna Franca , Solimeno Luigi Piero , Martinoli Carlo , Rocino Angiola , Pasta Gianluigi ,   Italian Association of Haemophilia Centres Musculoskeletal Working Group
Published: December 2021

Although synovitis is recognized as a marker of joint disease activity, its periodic assessment is not included in routine clinical surveillance of patients with haemophilia (PwH). In order to evaluate the current knowledge and to identify controversial issues, a preliminary literature search by the Musculoskeletal Committee of the Italian Association of Haemophilia Centres (AICE) has been conducted. Statements have been established and sent to the Italian AICE members to collect their level of agreement or disagreement by a Delphi process. Thirty‐seven consensus recommendations have been drafted. We found a general agreement on the indication to consider the presence of synovitis as a marker of joint disease activity in PwH. Accordingly, there was agreement on the indication to search for synovitis both in patients reporting joint pain and in asymptomatic ones, recognizing ultrasound as the most practical imaging technique to perform periodic joint screening. Interestingly, after detection of synovitis, there was agreement on the indication to modify the therapeutic approach, suggesting prophylaxis in patients treated on demand and tailoring treatment in patients already under prophylaxis. Whereas the need of an early consultation with a physiotherapist is recommended for PwH affected by chronic synovitis, the exact timing for an orthopaedic surgeon consultation is currently unknown.
Objects that induce face pareidolia are prioritized by the visual system
Authors: Caruana Nathan , Seymour Kiley
Published: December 2021

The human visual system has evolved specialized neural mechanisms to rapidly detect faces. Its broad tuning for facial features is thought to underlie the illusory perception of faces in inanimate objects, a phenomenon called face pareidolia. Recent studies on face pareidolia suggest that the mechanisms underlying face processing, at least at the early stages of visual encoding, may treat objects that resemble faces as real faces; prioritizing their detection. In our study, we used breaking continuous flash suppression (b‐CFS) to examine whether the human visual system prioritizes the detection of objects that induce face pareidolia over stimuli matched for object content. Similar to previous b‐CFS results using real face stimuli, we found that participants detected the objects with pareidolia faces faster than object‐matched control stimuli. Given that face pareidolia has been more frequently reported amongst individuals prone to hallucinations, we also explored whether this rapid prioritization is intact in individuals with schizophrenia, and found evidence suggesting that it was. Our findings suggest that face pareidolia engages a broadly tuned mechanism that facilitates rapid face detection. This may involve the proposed fast subcortical pathway that operates outside of visual awareness.
Synthesis of ring opening of evodiamine derivatives and evaluation on their biological activity
Authors: Guo Weihang , Wang Xianheng , Zhang Jidong , Zhang Tingting , Lv Hongfeng , Zhao Changkuo
Published: December 2021

As a main bioactive component extracted from Evodiae fructus, evodiamine has a variety of pharmacological activities. In this paper, evodiamine was chosen as starting material to react with different halides. Upon treatment of TFA, a series of novel ring‐opening evodiamine derivatives 3a–o were successfully synthesized in a moderate to high yields. These obtained compounds exhibit a moderate to good antitumor activity against MGC803 and SW480 in vitro test by MTT assay. The results showed that hexyl substituted evodiamine derivative (3j, R=hexyl) has a strong antitumor activity against MGC803 and SW480.
Radiolabeling, characterization, and preclinical evaluation of plazomicin: A potential tracer for bacterial infection
Authors: El‐kawy O. A. , Abdelaziz G. , Abdel‐Razek A. S.
Published: December 2021

In this study, 99mTc–plazomicin, a new radio‐antibiotic complex, was prepared specifically for bacterial infection localization and monitoring. Factors affecting the labeling reaction were studied and optimized to obtain a high yield (98.8 ± 0.2%). In silico, radiochemical and physicochemical characterization and biodistribution were performed to assess the complex aptness as a radiopharmaceutical. The complex was biologically evaluated in vitro using bacteria and in vivo using different inflammation models (sterile, bacterial, and fungal). Uptake in the bacterial model was highest (7.8 ± 0.3%). Results indicated that the technetium label did not alter the antibiotic biological behavior and backed the usefulness of 99mTc‐plazomicin as a potential tracer.
An eye-opening case of periorbital oedema: a clinicodiagnostic dilemma
Authors: Hegde Pallavi , Venugopal Madhumitha , Ramesh Sandhiya , Pai Kanthilatha , Shetty Rachan , Rao Raghavendra
Published: December 2021

Cutaneous metastasis (CM), a rare occurrence, can produce a variety of skin lesions. Signet-ring cell carcinoma (SRCC) is a very aggressive tumour with low survival rate irrespective of location. We report a case of SRCC with CM presenting with asymptomatic progressive unilateral angio-oedema-like findings. A high index of suspicion and low threshold for biopsy are crucial for early diagnosis of CM as the prognosis is poor, especially when the primary cancer is SRCC.
Low-dose tofacitinib with 308-nm excimer therapy successfully induced repigmentation in patients with refractory vitiligo
Authors: Fang Wei-Cheng , Lin Sheng-Yiao , Huang Shu-Mei , Lan Cheng-Che E.
Published: December 2021

Combining low-dose tofacitinib with 308-nm excimer may be an effective treatment for patients with nonsegmental vitiligo who were refractory to conventional therapies.
Factors affecting sensitization following kidney allograft failure
Authors: Garg Neetika , Viney Kelley , Burger John , Hidalgo Luis , Parajuli Sandesh , Aziz Fahad , Mohamed Maha A. , Djamali Arjang , Mandelbrot Didier A.
Published: December 2021

Introduction

Management of immunosuppression in a kidney transplant recipient with a failed allograft is complex; continuation carries infectious and metabolic risks, and discontinuation can lead to sensitization.

Methods

We evaluated risk factors for sensitization in 89 kidney or simultaneous kidney‐pancreas recipients, whose kidney transplant failed after January, 2013 and who were subsequently re‐evaluated for kidney transplantation.

Results

Among recipients with pre graft failure cPRA < 50%, calcineurin inhibitor (CNI) continuation (OR .11, P = .003) and steroid continuation (OR .17, P = .04) were associated with significantly lower odds of developing an absolute increase in cPRA of ≥50%. Each additional HLA mismatch was associated with OR of 2.16 (P = .02). CNI use was associated with OR of .09 (P = .001) for increase in cPRA to ≥80% if pre graft failure cPRA was <50%, and OR of .08 (P = .02) for increase in cPRA to ≥98% if pre graft cPRA was <80%. Anti‐metabolites were continued more often among recipients who had a <50% increase (P = .006); however, the association was lost on multivariate analyses. Weaning off immunosuppression and higher number of HLA mismatches are associated with greater likelihood of sensitization.

Conclusion

While both CNI and steroid continuation conferred some protection against increase in cPRA, CNI continuation was the only factor protecting against becoming highly sensitized.
Benefits of both physical assessment and electronic health record review to assess frailty prior to heart transplant
Authors: Lee Yoon Kyung , Shukman Marina , Biniwale Reshma , Ardehali Abbas , Kamath Megan , Nsair Ali , Schaenman Joanna M. , Goldwater Deena
Published: December 2021

Introduction

Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown.

Methods

This single‐center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart‐review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep.

Results

We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P = .043, P < .001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P = .022; P = .002) and not being transplanted (P = .026; P = .008). Higher frailty by SPPB and FFP was also associated with mortality (P = .010; P = .025).

Conclusion

SPPB and chart‐review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations.
Cardiac transplantation after heparin‐induced thrombocytopenia: A systematic review
Authors: Jimenez Diana C. , Warner Eric D. , Ahmad Danial , Rosen Jake L. , Al‐Rawas Nawar , Morris Rohinton J. , Alvarez Rene , Rame J. Eduardo , Entwistle John W. , Massey H. Todd , Tchantchaleishvili Vakhtang
Published: December 2021

Purpose

Heparin‐induced thrombocytopenia (HIT) presents a unique challenge in patients requiring orthotopic heart transplantation (OHT). We sought to pool the existing evidence in a systematic review.

Methods

Electronic search was performed to identify all relevant studies on OHT in patients with HIT. Patient‐level data for 33 patients from 21 studies were extracted for statistical analysis.

Results

Median patient age was 51 [IQR 41, 55] years, with 75.8% (25/33) males. All patients had a clinical diagnosis of HIT, and anti‐PF4/Heparin antibodies were positive in 87.9% (29/33). Median lowest reported platelet count was 46 × 109/L [27.2, 73.5]. Intraoperatively, 61% (20/33) of patients were given unfractionated heparin (UFH), while 39% (13/33) were given alternative anticoagulants. The alternative agent subgroup required more antifibrinolytics [54% (7/13) vs 10% (2/20), P = .02] and clotting factors [69.2% (9/13) vs 15.0% (3/20), P < .01]. Perioperative thrombosis occurred more [53.8% (7/13) vs 0% (0/20, P < .01) in alternate agent subgroup. More patients in the alternate agent subgroup required post‐operative transfusions [54% (7/13) vs 0% (0/20), P < .01]. Thirty‐day mortality of 15.2% (5/33) was comparable between the subgroups.

Conclusion

Heparin use during OHT may be associated with less adverse effects compared to use of other anticoagulants with no difference in 30‐day mortality.
A longitudinal study among young adults into the predictive effect of perceived efficacy of behavioural strategies and the moderating role of drinking motives on use of protective behavioural strategies
Authors: González‐Ponce Bella M. , Carmona‐Márquez José , Díaz‐Batanero Carmen , Vera Belén del Valle , Pilatti Angelina , Fernández‐Calderón Fermín
Published: December 2021

Introduction

Although protective behavioural strategies (PBS) have shown to be effective in minimising alcohol‐related negative consequences, research on the explanatory factors of their use is very scarce. Perceived efficacy has been demonstrated to be one of the most relevant explanatory factors in the use of health‐related protective behaviours. The present study prospectively examines the relationship between the perceived efficacy of PBS in reducing alcohol‐related negative consequences and the use of PBS in a community‐based sample of young adults. In addition, the moderating role of drinking motives in this relationship is also examined.

Methods

Prospective design with a baseline assessment and a 2‐month follow up. Using a targeted sampling procedure, 339 young adults were recruited from the community [mean age: 21.1 (SD = 2.21); female = 50.7%] and completed questionnaires to measure perceived efficacy of PBS and drinking motives at baseline and PBS use at follow up.

Results

Perceived efficacy of PBS at baseline was positively associated with PBS use at follow up, and these relationships were weaker as social, enhancement and coping motives scores increased.

Discussion and Conclusions

Our findings support the need to include the perceived efficacy of PBS to reduce alcohol‐related negative consequences in future interventions aimed at promoting PBS use. Moreover, these interventions should be personalised according to the initial levels of participants' drinking motives, incorporating elements that allow for neutralising their negative effects on PBS use (e.g. training in coping skills for those with strong coping motives).
Risk of cancer in young and middle‐aged adults with childhood‐onset type 1 diabetes in Sweden—A prospective cohort study
Authors: Fredriksson Marie , Persson Emma , Dahlquist Gisela , Möllsten Anna , Lind Torbjörn
Published: December 2021

Aims/hypothesis

In persons with type 1 diabetes, the risk of cancer remains controversial. We wanted to examine the excess risk of cancer in a large population‐based cohort diagnosed with type 1 diabetes before 15 years of age.

Study population and methods

From 1 July 1977 to 31 December 2013, we prospectively and on a national scale included 18,724 persons (53% men) with childhood‐onset type 1 diabetes. For each person with type 1 diabetes, we selected four referents, matched for the date at birth and municipality of living at the time when the case developed diabetes. Cases and referents were linked to national registers of cancer and of the cause of death.

Results

A total of 125 persons (61% women) with diabetes had 135 different cancers, all diagnosed after the diabetes diagnosis. The median duration from diabetes diagnosis to first cancer diagnosis was 19 years (interquartile range 10‐26). The median age at cancer diagnosis in the diabetes group was 28 years (interquartile range 20‐35). The overall standardized incidence ratio (95%), using the Swedish general population as referents for women with diabetes was 1.28 (1.02, 1.58) and when comparing women with diabetes with matched referents, we found a hazard ratio of 1.42 (1.10, 1.85). No elevated risk was seen for men. Cancers of the breast and testis were the most common types in women and men respectively.

Conclusions

Women with childhood‐onset type 1 diabetes had a small but significantly elevated risk of cancer. No such tendency was seen for men. The reason behind this is unclear.
Native mitral valve staphylococcus endocarditis with a very unusual complication: Ruptured posterior mitral valve leaflet aneurysm
Authors: Maidman Samuel D. , Kiefer Nicholas J. , Bernard Samuel , Freedberg Robin S. , Rosenzweig Barry P. , Bamira Daniel , Vainrib Alan F. , Ro Richard , Neuburger Peter J. , Basu Atreyee , Moreira Andre L. , Latson Larry A. , Loulmet Didier F. , Saric Muhamed
Published: December 2021

Infective endocarditis (IE) is a life‐threatening disease associated with in‐hospital mortality of nearly one in five cases. IE can destroy valvular tissue, which may rarely progress to aneurysm formation, most commonly at the anterior leaflet in instances of mitral valve involvement. We present a remarkable case of a patient with IE and a rare complication of a ruptured aneurysm of the posterior leaflet of the mitral valve. Two‐ and Three‐dimensional transesophageal echocardiography, intra‐operative videography, and histopathologic analysis revealed disruption at this unusual location–at the junction of the P2 and P3 scallops, surrounded by an annular abscess.
Prenatal diagnosis, management, and postnatal outcome of a fetus with massive cardiomegaly secondary to placenta chorioangioma
Authors: Karmegaraj Balaganesh , Ibrahim Syed , Razeen Mohamed , Premasudha Venkatanarayanan , Rajesh Arasi
Published: December 2021

Chorioangiomas are the most common non‐trophoblastic benign vascular tumor of the placenta, highly associated with perinatal death rate. Herewith, we are reporting the prenatal diagnosis, management and postnatal outcome of a fetus referred at 33 weeks gestation with massive cardiomegaly secondary to placenta chorioangioma.
Unequivocal interpretation of dobutamine stress echocardiography in low‐flow, low‐gradient aortic stenosis by right parasternal view
Authors: Setti Martina , Nistri Stefano , Rossi Andrea , Mantovani Francesca , Ribichini Flavio L. , Benfari Giovanni
Published: December 2021

We present the case of a 77‐years‐old man with aortic valve stenosis (AS) and reduced left ventricular ejection fraction, in whom right parasternal view provided the best hemodynamic evaluation of AS severity during dobutamine stress echocardiography