bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Cognitive Behavioral Therapy for Insomnia for the Treatment of Child and Adolescent Anxiety and Depression
Authors: Reddy Abhishek , Mansuri Zeeshan , Vadukapuram Ramu , Shah Kaushal , Thootkur Mounica , Trivedi Chintan
Published: February 2023

Cognitive behavioral therapy for insomnia (CBT-I) has shown promising results in the adult population. However, there is not enough evidence for children and adolescents. Hence, we evaluated the current evidence of CBT-I in the treatment of anxiety and depression in children and adolescents. Published randomized clinical trials published before June 2020 were searched from PubMed, Cochrane Library of database, clinicaltrials.gov, and Google Scholar. Out of seven included studies, six studies assessed the effect of CBT-I on depression, and five assessed the effect on anxiety. In this review, most studies in this review showed a strong effect of CBT-I on symptoms of depression. Although a positive effect of CBT-I on anxiety was noted, only a small number of studies have considered this management. These findings should be considered preliminary, and further large-scale studies are warranted to further explore this finding further.
Clinical Characteristics of Melancholic and Nonmelancholic Depressions
Authors: Valerio Marina P. , Lomastro Julieta , Igoa Ana , Martino Diego J.
Published: February 2023

This study aimed to compare clinical-demographic features of melancholic and nonmelancholic depressions. We included 141 depressed inpatients classified as melancholic and nonmelancholic by the Sydney Melancholia Prototype Index (SMPI) andDiagnostic and Statistical Manual of Mental Disorders, 5th Edition(DSM-5) criteria. Results were controlled for confounders, including severity measures. Melancholic patients by both diagnostic systems were more severely depressed and presented more psychotic symptoms, neurological soft signs, and psychomotor disturbances. Melancholic patients classified by the SMPI were also older at illness onset and had fewer suicide attempts. After controlling for confounders, although all differences remained significant for SMPI diagnosis, theDSM-5diagnosis of melancholia was only associated with further impaired motor sequencing. The results obtained with the SMPI support the hypothesis that melancholia has clinical features qualitatively different from those of nonmelancholic depressions. Contrarily, theDSM-5specifier seems to reflect the severity of depressive episodes rather than core clinical features of melancholia.
The Role of Emotion Dysregulation in the Relationship Between Sleep Disturbances and PTSD Symptom Severity
Authors: Dolan Megan , Slavish Danica C. , Weiss Nicole H. , Contractor Ateka A.
Published: February 2023

Emotion dysregulation is implicated in the development, maintenance, and treatment of sleep disturbances and posttraumatic stress disorder (PTSD) separately. However, few studies have assessed interactions among these variables. To address this gap, this study examined whether the associations of sleep quality and sleep quantity with PTSD severity were stronger at higher levels of negative and positive emotion dysregulation in a community sample of 199 trauma-exposed individuals. This study found that both poorer sleep quality and lower sleep quantity were associated with greater PTSD severity at low to average (but not high) levels of negative emotion dysregulation. Positive emotion dysregulation did not moderate the relationships between sleep quality or quantity and PTSD severity. Exploratory additive multiple moderation analyses showed significant associations between poorer sleep quality and lower sleep quantity with greater PTSD severity at low to average levels of negative emotion dysregulation, coupled with any level of positive emotion dysregulation. Findings inform theoretical perspectives on the sleep-PTSD relationship and clinical applications of targeting emotion dysregulation in the treatment of sleep disturbances and PTSD symptoms for trauma-exposed individuals.
Outcome of tibial shaft fractures treated with the SIGN FIN nail at Addis Ababa Emergency, Burn, and Trauma Hospital (AaEBT) Addis Ababa, Ethiopia
Authors: Tesso Cheru Beyene , Zirkle Lewis G. , Worku Abiy , Tilahun Getachew , Kebede Samuel , Desta Tilahun
Published: February 2023

Objectives:

To determine the outcome of tibial fractures treated with the SIGN FIN nail.

Study Design:

Retrospective case series study.

Study Setting:

Trauma center.

Methods and Materials:

We included 14 patients aged 18–51 years with 16 tibial fractures in this study. Patients were followed clinically and radiographically, and the minimum time followed was 6 months. Johner and Wruhs criteria with modification were used to assess the outcome.

Result:

There were 11 male (78.6%) and three female (21.4%) patients. The mean age was 32.44 ± 8.98 (range 18–51) years. The right-sided tibia was injured in six as compared with the left side in four, and four patients had bilateral injuries. Eight (50%) fractures were closed fractures, whereas the rest eight (50%) were open types of fractures. Among the latter, half (n = 4; 50%) fractures were Gustilo type II fractures, while three (37.5%) fractures were Gustilo type III fractures, and one (12.5%) patient had a Gustilo type I fracture. All patients had radiologic union. There were no infections or secondary surgery for any reason. Excellent, good, and fair results were achieved in 62.5%, 25%, and 12.5%, respectively. All patients were able to return to their preinjury activity except two patients.

Conclusion:

SIGN FIN nail is an option for treating tibial shaft fractures with good outcomes and few complications in selected fractures.

Level of evidence:

Level IV
Long-term ultrasonographic and histologic changes in acellular dermal matrix in implant-based breast reconstructions
Authors: Lee Jun Ho , Choi Bong Gyu , Lee Won Seob , Seo Min-Gi , Park Bo-Yoon , Kim Young Seon , Park Do Young , Kim Il-Kug
Published: February 2023

Background:

Acellular dermal matrix (ADM) is composed of extracellular matrix (ECM) and is widely used in implant-based breast reconstructions. However, long-term changes in the ADM around implants have not been established. This study aimed to investigate long-term changes in the ADM covering breast implants using serial ultrasound (US) and histologic evaluations.

Methods:

We evaluated the US results of 144 patients who underwent implant-based breast reconstructions with ADM coverings. The US results obtained within 18 months of surgery and those obtained 5 years postoperatively were analyzed to determine the change in the ADM thickness. For histologic analysis, the ADM was harvested from 30 patients who underwent secondary breast surgery. Histologic features of the ECM and cellular components within the ADM were compared at specific intervals from ADM implantation and the second operation (early ADM group: <18 months, late ADM group: >5 years postoperatively).

Results:

The ADM thickness on US examination significantly decreased in the late ADM compared with that in the early ADM (p< 0.001). Histologic analyses revealed that the late ADM group had less thickness with lower ECM levels than the early ADM group had. Increased infiltration of host cells such as vascular endothelial cells, myofibroblasts, and immune cells occurred in the late ADM.

Conclusions:

Implanted ADMs underwent gradual thinning over time, in addition to ECM reduction and infiltration of host cells. These findings are useful in understanding the natural course of ADMs currently used in implant-based breast reconstructions.
Gender Surgery in Adolescents and Young Adults: A Review of Ethical and Surgical Considerations
Authors: Robinson Isabel S. , Carswell Jeremi M. , Boskey Elizabeth , Agarwal Cori A. , Brassard Pierre , Bélanger Maud , Zhao Lee C. , Bluebond-Langner Rachel
Published: February 2023

BACKGROUND:

The incidence of transgender adolescents seeking gender affirming surgery (GAS) in increasing. Surgical care of the adolescent transgender patient is associated with several unique technical, legal, and ethical factors. The authors present a review of the current literature on gender affirming surgery for individuals under the age of legal majority and propose directions for future research.

METHODS:

A scoping review of recent literature was performed to assess evidence on gender affirming surgery in individuals under the age of legal majority. Papers were included that examined either ethical or technical factors unique to pediatric GAS. Study characteristics and conclusions were analyzed in conjunction with expert opinion.

RESULTS:

Twelve papers were identified meeting inclusion criteria. Ten of these papers discussed ethical challenges in adolescent GAS, seven papers discussed legal challenges, and five papers discussed technical challenges. Ethical discussions focused on the principles of beneficence, nonmaleficence, and autonomy. Legal discussions centered on informed consent and insurance coverage. Technical discussions focused on the impact of puberty blockade on natal tissue.

CONCLUSIONS:

Surgical care of the adolescent transgender patient involves important ethical, legal, and technical considerations that must be addressed by the clinical team. As the population of individuals seeking GAS after puberty blockade increases, future research is needed describing functional and psychosocial outcomes in these individuals.
Photon Counting Detector CT-Based Virtual Noniodine Reconstruction Algorithm for In Vitro and In Vivo Coronary Artery Calcium Scoring: Impact of Virtual Monoenergetic and Quantum Iterative Reconstructions
Authors: Fink Nicola , Zsarnoczay Emese , Schoepf U. Joseph , Griffith Joseph P. , Wolf Elias V. , O'Doherty Jim , Suranyi Pal , Baruah Dhiraj , Kabakus Ismail M. , Ricke Jens , Varga-Szemes Akos , Emrich Tilman
Published: February 2023

Objectives

The aim of this study was to evaluate the impact of virtual monoenergetic imaging (VMI) and quantum iterative reconstruction (QIR) on the accuracy of coronary artery calcium scoring (CACS) using a virtual noniodine (VNI) reconstruction algorithm on a first-generation, clinical, photon counting detector computed tomography system.

Materials and Methods

Coronary artery calcium scoring was evaluated in an anthropomorphic chest phantom simulating 3 different patient sizes by using 2 extension rings (small: 300 × 200 mm, medium: 350 × 250 mm, large: 400 × 300 mm) and in patients (n = 61; final analyses only in patients with coronary calcifications [n = 34; 65.4 ± 10.0 years; 73.5% male]), who underwent nonenhanced and contrast-enhanced, electrocardiogram-gated, cardiac computed tomography on a photon counting detector system. Phantom and patient data were reconstructed using a VNI reconstruction algorithm at different VMI (55–80 keV) and QIR (strength 1–4) levels (CACSVNI). True noncontrast (TNC) scans at 70 keV and QIR “off” were used as reference for phantom and patient studies (CACSTNC).

Results

In vitro and in vivo CACSVNIshowed strong correlation (r> 0.9,P< 0.001 for all) and excellent agreement (intraclass correlation coefficient > 0.9 for all) with CACSTNCat all investigated VMI and QIR levels. Phantom and patient CACSVNIsignificantly increased with decreasing keV levels (in vitro: from 475.2 ± 26.3 at 80 keV up to 652.5 ± 42.2 at 55 keV; in vivo: from 142.5 [7.4/737.7] at 80 keV up to 248.1 [31.2/1144] at 55 keV;P< 0.001 for all), resulting in an overestimation of CACSVNIat 55 keV compared with CACSTNCat 70 keV in some cases (in vitro: 625.8 ± 24.4; in vivo: 225.4 [35.1/959.7]). In vitro CACS increased with rising QIR at low keV. In vivo scores were significantly higher at QIR 1 compared with QIR 4 only at 60 and 80 keV (60 keV: 220.3 [29.6–1060] vs 219.5 [23.7/1048]; 80 keV: 152.0 [12.0/735.6] vs 142.5 [7.4/737.7];P< 0.001). CACSVNIwas closest to CACSTNCat 60 keV, QIR 2 (+0.1%) in the small; 55 keV, QIR 1 (±0%) in the medium; 55 keV, QIR 4 (−0.1%) in the large phantom; and at 60 keV, QIR 1 (−2.3%) in patients.

Conclusions

Virtual monoenergetic imaging reconstructions have a significant impact on CACSVNI. The effects of different QIR levels are less consistent and seem to depend on several individual conditions, which should be further investigated.
Combined Ablation and Resection for Colorectal Liver Metastases in the Minimally Invasive Surgical Era
Authors: Vandeputte Mathieu , Saveyn Thiebault , Lutin Bart , De Meyere Celine , Parmentier Isabelle , D’Hondt Mathieu
Published: February 2023

Background:

Thermal ablation is an accepted treatment modality for small and central liver tumors. In extensive colorectal liver metastatic disease (CRLM), hepatectomy can be combined with ablation, resulting in a parenchymal-sparing strategy. This may increase salvageability rates in case of recurrence.

Methods:

All patients with advanced CRLM that underwent combined ablation and resection between April 2012 and April 2021, were retrospectively analyzed from a prospectively maintained database. Primary endpoints include postoperative 30-day morbidity and ablation-site recurrence (ASR). The surgical approaches were compared. Ablated lesions were screened for ASR on postoperative follow-up imaging.

Results:

Of 54 patients that underwent combined ablation and resection, 32 (59.3%) were performed through a minimally invasive approach. Eleven (20.4%) were minor resections, 32 (59.3%) were technically major and 11 (20.4%) were anatomically major resections. Twelve complications occurred (22.2%), among which 2 (3.8%) major complications (Clavien-Dindo ≥IIIa). Ninety-day mortality rate was 1.9%. Out of 82 ablated lesions, 6 ASRs (11.1%) occurred. Median blood loss was significantly lower in the minimally invasive group, compared with open [90 mL (32.5 to 200) vs. 200 mL (100 to 400), P=0.005]. Pringle maneuver was significantly performed less in the minimally invasive group [8 (25.0%) vs. 16 (72.7%), P=0.001], but took more time [36.1 min (±15.6) vs. 21.6 (±9.9); P=0.011]. Short-term (1 y) overall and disease-free survival were respectively 81.4% and 50.0%.

Conclusion:

Combining microwave ablation and liver resection is a feasible and safe parenchymal-sparing technique, through both minimally invasive and open approach for treating extended CRLM disease. It has a low ablation-related complication rate and acceptable ablation-site recurrence rate.
The Role of Pretransplant Infections in Pediatric Receiving LDLT in Indonesia: A 7-y Retrospective Study
Authors: Alatas Fatima Safira , Karyanti Mulya Rahma , Nugraha Marcel Aditya , Tartila Tartila , Pudjiadi Antonius Hocky
Published: February 2023

Background.

Liver transplantation is the definitive treatment for pediatric end-stage liver disease. Infections posttransplantation might significantly affect the outcome of the surgery. This study aimed to identify the role of pretransplant infection among children who underwent living donor liver transplantation (LDLT) in Indonesia.

Methods.

This is an observational, retrospective cohort study. A total of 56 children were recruited between April 2015 and May 2022. Patients were categorized into 2 according to the presence of pretransplantation infections requiring hospitalization before the surgery. Diagnosis of posttransplantation infection was observed for up to 1 y based on the clinical features and laboratory parameters.

Results.

The most common indication for LDLT was biliary atresia (82.1%). Fifteen of 56 patients (26.7%) had a pretransplant infection, whereas 73.2% of patients were diagnosed with a posttransplant infection. There was no significant association between pretransplant and posttransplant infection in all 3-time points (≤1 mo, 2–6 mo, and 6–12 mo). The most common organ involvement posttransplantation was respiratory infections (50%). The pretransplant infection did not significantly affect posttransplant bacteremia, length of stay, duration of mechanical ventilation, initiation of enteral feeding, hospitalization cost, and graft rejection.

Conclusions.

Our data showed that pretransplant infections did not significantly affect clinical outcomes in post-LDLT procedures. A prompt and sufficient diagnosis and treatment before and after the LDLT procedure is the best way to obtain an optimal outcome.
Borderline Personality Disorder and Outcome of Electroconvulsive Therapy in Patients With Depression
Authors: Nicolini Alain P. , Sienaert Pascal
Published: February 2023

Major depressive disorder (MDD) commonly coincides with borderline personality disorder (BPD), aggravating depressive symptom severity and reducing the odds of responding to antidepressant treatments. In this systematic review, we summarize the available evidence assessing the question whether the presence of BPD reduces the response to electroconvulsive therapy (ECT) in individuals with MDD.

We conducted a systematic literature search (up to December 2021) without language restriction, using the PubMed/MEDLINE, Web of Science (Core Collection), Embase, and Cochrane Library databases, for prospective and retrospective studies, which assessed the efficacy of ECT in patients with MDD and comorbid BPD.

Of the 2548 records screened, 6 articles were selected, 2 of which were based on the same population, leading to 5 included articles. The included studies are reporting on 3465 patients with MDD, of which 1206 had a comorbid BPD. Five of the 6 studies found a less robust response to ECT in patients with MDD and BPD compared with those without BPD.

Our results suggest that, in patients with MDD, the presence of BPD is associated with a less robust acute response to ECT. Patients with BPD, however, showed a significant response to ECT in all of the included studies. More longitudinal studies with higher accuracy in BPD diagnosis are needed. Although a comorbid BPD seems to decrease the efficacy of ECT for MDD, ECT remains an effective treatment option in this severely ill patient group.
Moniliella zaluziensis sp. nov., a black yeast related to fruit trees of the Rosaceae family
Authors: Pipiková Jana , Horváthová Ágnes , Schusterová Hana , Vadkertiová Renáta
Published: February 2023

Our previous studies focused on the diversity of yeasts related to the aboveground parts of fruit trees, as well as the soil adjacent to these trees, located in the south-west of Slovakia. During these studies, we isolated two Moniliella strains: CCY 11-1-1T from the blossoms of a peach tree (Prunus persica) and CCY 11-1-2 from the soil adjacent to a pear tree (Pyrus communis), both found in the Malé Zálužie locality. The sequences of the D1/D2 domain of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region were identical in both strains. They differed only by two nucleotide substitutions in the segment of the gene of translation elongation factor one alpha (TEF-1α). Phylogenetic analysis demonstrated that strains CCY 11-1-1T and CCY 11-1-2 formed a separate species in the clade of insect-associated members of the genus Moniliella. The strains differed from the closest species Moniliella oedocephalis by 23 nucleotide substitutions and 12 indels in the D1/D2 domain, more than 6 % in the ITS region (31 nt and 25 indels) and by 44 nt in the segment of TEF-1α. Therefore, these two strains are recognized as belonging to a novel species, for which we have proposed the name Moniliella zaluziensis sp. nov., derived from the locality of their origin, Malé Zálužie. The type strain of M. zaluziensis sp. nov. is CCY 11-1-1T.
Aspergillus verrucosus sp. nov., a xerophilic species isolated from house dust and honey in Japan
Authors: Hagiuda Ryo , Itagaki Tadashi , Hirose Dai
Published: February 2023

Three strains of a xerophilicAspergillusspecies were isolated from house dust and honey in Japan. A molecular phylogenetic analysis based on the combined dataset for four regions (internal transcribed spacer rDNA, calmodulin, β-tubulin, and RNA polymerase II second largest subunit) revealed that the strains formed an independent lineage, sister toAspergillus halophilicusclassified in sectionRestricti. Morphological comparisons show that the strains differ fromA. halophilicusin three aspects: (i) the size of cleistothecia, as well as the surface structure and size of ascospores, (ii) the ability to grow on Harrold’s agar and dichloran 18 % glycerol agar, and (iii) the lack of conidiophore formation on potato dextrose agar +20 % NaCl. These strains could be clearly distinguished from all knownAspergillussectionRestrictispecies. Therefore, we consider it to be a novel species and propose the nameAspergillus verrucosussp. nov. (NBRC 115547T).
Aliiroseovarius subalbicans sp. nov. and Aliiroseovarius sediminis sp. nov., isolated from marine sediment
Authors: Zheng Rui , Ping Xiu-Ya , Fang Qi , Lu De-Chen , Du Zong-Jun , Gong Ya
Published: February 2023

Two novel strains (N1Y82T and N1F302T) were isolated from a marine sediment sample taken from the coastal zone of Weihai, PR China. Cells of the two strains were Gram-strain-negative, catalase-positive, oxidase-positive, non-motile and ovoid- to rod-shaped. Strain N1Y82T grew optimally at 16 °C, pH 7.5 and in the presence of 3.0 % (w/v) NaCl. Strain N1F302T grew optimally at 28 °C, pH 7.0–7.5 and in the presence of 2.0–2.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strains N1Y82T and N1F302T belonged to the genus

Aliiroseovarius

, and were mostly related to

Aliiroseovarius sediminilitoris

KCTC 23959T with sequence similarity of 96.5 and 97.1 %, respectively. For these two novel strains, C18 : 1 ω7c was the major fatty acid, ubiquinone 10 was the predominant respiratory quinone, and phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid and one unidentified phospholipid were the major polar lipids. The DNA G+C contents of strain N1Y82T and N1F302T were 61.3 and 59.0 %, respectively. Consequently, strains N1Y82T and N1F302T are considered to represent two novel species of the genus

Aliiroseovarius

, for which the names Aliiroseovarius subalbicans sp. nov. and Aliiroseovarius sediminis sp. nov. are proposed. The type strains are N1Y82T (=KCTC 82768T=MCCC 1H00524T) and N1F302T (=KCTC 82412T=MCCC 1H00525T), respectively.
Highly conserved composite transposon harbouring aerobactin iuc3 in Klebsiella pneumoniae from pigs
Authors: Kaspersen Håkon , Franklin-Alming Fiona Valerie , Hetland Marit A. K. , Bernhoff Eva , Löhr Iren H. , Jiwakanon Jatesada , Urdahl Anne Margrete , Leangapichart Thongpan , Sunde Marianne
Published: February 2023

Klebsiella pneumoniae

is an important opportunistic pathogen associated with severe invasive disease in humans. Hypervirulent

K. pneumoniae

, which are

K. pneumoniae

with several acquired virulence determinants such as the siderophore aerobactin and others, are more prominent in countries in South and South-East Asia compared to European countries. This

Klebsiella

pathotype is capable of causing liver abscesses in immunocompetent persons in the community.

K. pneumoniae

has not been extensively studied in non-human niches. In the present study,

K. pneumoniae

isolated from caecal samples (n=299) from healthy fattening pigs in Norway were characterized with regard to population structure and virulence determinants. These data were compared to data from a previous study on

K. pneumoniae

from healthy pigs in Thailand. Lastly, an in-depth plasmid study on

K. pneumoniae

with aerobactin was performed. Culturing and whole-genome sequencing was applied to detect, confirm and characterize

K. pneumoniae

isolates. Phylogenetic analysis described the evolutionary relationship and diversity of the isolates, while virulence determinants and sequence types were detected with Kleborate. Long-read sequencing was applied to obtain the complete sequence of virulence plasmids harbouring aerobactin. A total of 48.8 % of the investigated Norwegian pig caecal samples (n=299) were positive for

K. pneumoniae

. Acquired virulence determinants were detected in 72.6 % of the isolates, the most prominent being aerobactin (69.2 %), all of which were iuc3. In contrast, only 4.6 % of the isolates from Thailand harboured aerobactin. The aerobactin operon was located on potentially conjugative IncFIBK/FIIK plasmids of varying sizes in isolates from both countries. A putative, highly conserved composite transposon with a mean length of 16.2 kb flanked by truncated IS3-family IS407-group insertion sequences was detected on these plasmids, harbouring the aerobactin operon as well as several genes that may confer increased fitness in mammalian hosts. This putative composite transposon was also detected in plasmids harboured by

K. pneumoniae

from several countries and sources, such as human clinical samples. The high occurrence of

K. pneumoniae

harbouring aerobactin in Norwegian pigs, taken together with international data, suggest that pigs are a reservoir for

K. pneumoniae

with iuc3. Truncation of the flanking ISKpn78-element suggest that the putative composite transposon has been permanently integrated into the plasmid, and that it is no longer mobilizable.
RevGel-seq: instrument-free single-cell RNA sequencing using a reversible hydrogel for cell-specific barcoding
Authors: Komatsu Jun , Cico Alba , Poncin Raya , Le Bohec Maël , Morf Jörg , Lipin Stanislav , Graindorge Antoine , Eckert Hélène , Saffarian Azadeh , Cathaly Léa , Guérin Frédéric , Majello Sara , Ulveling Damien , Vayaboury Anaïs , Fernandez Nicolas , Dimitrova Dilyana , Bussell Xavier , Fourne Yannick , Chaumat Pierre , André Barbara , Baldivia Elodie , Godet Ulysse , Guinin Mathieu , Moretto Vivien , Ismail Joy , Caille Olivier , Roblot Natacha , Beaupère Carine , Liboz Alexandrine , Guillemain Ghislaine , Blondeau Bertrand , Walrafen Pierre , Edelstein Stuart
Published: February 2023

Progress in sample preparation for scRNA-seq is reported based on RevGel™-seq, a reversible-hydrogel technology optimized for samples of fresh cells. Complexes of one cell paired with one barcoded bead are stabilized by a chemical linker and dispersed in a hydrogel in the liquid state. Upon gelation on ice the complexes are immobilized and physically separated without requiring nanowells or droplets. Cell lysis is triggered by detergent diffusion, and RNA molecules are captured on the adjacent barcoded beads for further processing with reverse transcription and preparation for cDNA sequencing. As a proof of concept, analysis of PBMC using RevGel-seq achieves results similar to microfluidic-based technologies when using the same original sample and the same data analysis software. In addition, a clinically relevant application of RevGel-seq is presented for pancreatic islet cells. Furthermore, characterizations carried out on cardiomyocytes demonstrate that the hydrogel technology readily accommodates very large cells. Standard analyses are in the 10,000-input cell range with the current gelation device, in order to satisfy common requirements for single-cell research. A convenient stopping point after two hours has been established by freezing at the cell lysis step, with full preservation of gene expression profiles. Overall, our results show that RevGel-seq represents an accessible and efficient instrument-free alternative, enabling flexibility in terms of experimental design and timing of sample processing, while providing broad coverage of cell types.
Durable reprogramming of neutralising antibody responses following breakthrough Omicron infection
Authors: Lee Wen Shi , Tan Hyon-Xhi , Reynaldi Arnold , Esterbauer Robyn , Koutsakos Marios , Nguyen Julie , Amarasena Thakshila , Kent Helen E , Aggarwal Anupriya , Turville Stuart G , Taiaroa George , Kinsella Paul , Liew Kwee Chin , Tran Thomas , Williamson Deborah A , Cromer Deborah , Davenport Miles P , Kent Stephen J , Juno Jennifer A , Khoury David S , Wheatley Adam K
Published: February 2023

SARS-CoV-2 breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months post-infection. Both BA.1 and BA.2 infection robustly boosted neutralisation activity against the infecting strain while expanding breadth against other Omicron strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment ofde novoOmicron-specific B cells or antibodies. Modelling of neutralisation titres predicts that protection from symptomatic reinfection against antigenically similar strains will be remarkably durable, but is undermined by novel emerging strains with further neutralisation escape.

One sentence summary

Omicron breakthrough infection elicits durable neutralising activity by recalling cross-reactive vaccine-elicited memory B cells.
Training parameters and longitudinal adaptations that most strongly mediate walking capacity gains from high-intensity interval training post-stroke
Authors: Boyne Pierce , Miller Allison , Schwab Sarah M. , Sucharew Heidi , Carl Daniel , Billinger Sandra A. , Reisman Darcy S.
Published: February 2023

Background

Locomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, heart rate, blood lactate, step count) and to what extent walking capacity gains are the result of neuromotor versus cardiorespiratory adaptations.

Objective

Assess which training parameters and longitudinal adaptations most strongly mediate 6-minute walk distance (6MWD) gains from post-stroke HIIT.

Methods

The HIT-Stroke Trial randomized 55 persons with chronic stroke and persistent walking limitations to HIIT or MAT and collected detailed training data. Blinded outcomes included 6MWD, plus measures of neuromotor gait function (e.g. fastest 10-meter gait speed) and aerobic capacity (e.g. ventilatory threshold). This ancillary analysis used structural equation models to compare mediating effects of different training parameters and longitudinal adaptations on 6MWD.

Results

Net gains in 6MWD from HIIT versus MAT were primarily mediated by faster training speeds and longitudinal adaptations in neuromotor gait function. Training step count was also positively associated with 6MWD gains, but was lower with HIIT versus MAT, which decreased the net 6MWD gain. HIIT generated higher training heart rate and lactate than MAT, but aerobic capacity gains were similar between groups, and 6MWD changes were not associated with training heart rate, training lactate, or aerobic adaptations.

Conclusions

To increase walking capacity with post-stroke HIIT, training speed and step count appear to be the most important parameters to prioritize.
Repurposing chlorpromazine as add-on in the adjuvant phase of first-line glioblastoma therapeutic protocol in patients carrying hypo-/un-methylatedMGMTgene promoter: RACTAC, a Phase II multicenter single-arm clinical trial
Authors: Pace Andrea , Lombardi Giuseppe , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cestonaro Ilaria , Corrà Martina , Cerretti Giulia , Caccese Mario , Silvani Antonio , Gaviani Paola , Giannarelli Diana , Paggi Marco G.
Published: February 2023

Background

Glioblastoma (GBM) is a devastating brain tumor with poor prognosis, characterized by rapid growth and invasion into surrounding brain tissue. It is a hard-to-treat cancer and represents an unmet medical need. In recent years, there has been a growing interest in developing novel approaches to improve the outcomes of GBM patients; among these, drug repurposing. Our preclinical studies identified the antipsychotic chlorpromazine (CPZ) as an important modulator of signal transduction and energy metabolism in GBM cells, so we embarked on a Phase II clinical trial in which CPZ has been added to the standard disease treatment.

Methods

With these assumptions, we started a multicenter phase II clinical trial on newly diagnosed GBM patients carrying hypo-/un-methylatedMGMTgene promoter by adding CPZ to temozolomide (TMZ) in the adjuvant phase of the standard first-line therapeutic protocol RACTAC schedule). Primary endpoints: Progression-Free Survival (PFS) and Combination treatment toxicity. Secondary endpoints: Overall Survival (OS) and Quality of Life (QoL)

Results

The RACTAC schedule showed an overall clinical benefit in GBM patients carrying hypo-/un-methylatedMGMTgene promoter. When compared with historical cohorts, these patients displayed longer PFS, with toxicity described as a dose-dependent sedation and liver toxicity, both expected. One case of severe liver toxicity has been reported. OS and QoL are still under evaluation.

Conclusions

This clinical trial confirms the anticancer properties of CPZ, as described in several preclinical studies. In addition, the RACTAC study can be considered at least as a proof-of-concept in demonstrating the effectiveness of interfering with the well-described oncogenic monoamine signaling between neurons and GBM.
Nano Sensing for Early Diagnosis of Pancreatic Cancer
Authors: Krishna Sidarth , McClelland Arthur , Zeng Tingying Helen
Published: February 2023

Pancreatic Cancer is becoming the second leading cause of cancer deaths, mainly attributed to late diagnosis. Surgical resection remains the only plausible treatment for curing patients of this cancer, but this is only possible when the cancer is localized making early detection vital. Currently, the most common early diagnostic method is the tri-phasic pancreatic-protocol CT scan. This method however has a low accuracy and specificity making it an ineffective early diagnostic. This purpose of this research was to develop a non-invasive, fast, and highly sensitive early diagnostic method for pancreatic cancer through the applications of nanotechnology. Surface Enhanced Raman Spectroscopy (SERS) is an innovative nano sensing method which results from plasmonic effect through molecules interacting with the surface of metal nanoparticles. This is a new method for trace biomarker detections and shows great potential to be an early nano-diagnostic method for Pancreatic cancer. This project uses Leucine as a biomarker for the demonstration of SERS for early pancreatic cancer detection. This is because recent studies show that Leucine has linked its overexpression with pancreatic cancer; studies have found a specificity of 100% with the use of Leucine and early diagnosis 2 to 5 years earlier than current diagnostic methods for pancreatic cancer. The parameters for SERS enhancement were optimized for the detection of Leucine using 20 nm Ag NPs. Predictive curves with linear fits were generated from an analysis of feature peaks giving the highest sensitivity for trace concentrations. This new finding shows the promising development of an early diagnostic method that is non-invasive, efficient and highly accurate for pancreatic cancer through SERS nano sensing.
Treatment of Slow-flow After Primary Percutaneous Coronary Intervention With Flow-mediated Hyperemia. The Randomized RAIN-FLOW Study
Authors: Gomez-Lara Josep , Gracida Montserrat , Rivero Fernando , Gutiérrez Alejandro , Muntané-Carol Guillem , Romaguera Rafael , Fuentes Lara , Marcano Ana , Roura Gerard , Ferreiro José Luis , Teruel Luis , Brugaletta Salvatore , Alfonso Fernando , Comín-Colet Josep , Gomez-Hospital Joan-Antoni
Published: February 2023

Background

ST-segment Elevation Myocardial Infarction (STEMI) complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have shown to improve the Thrombolysis In Myocardial Infarction (TIMI) flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 ml/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologicvs. flow-mediated hyperemia in STEMI patients complicated with no reflow.

Methods

STEMI patients with no reflow were randomized to receive either adenosine or nitroprussidevs. flow-mediated hyperemia. The angiographic corrected TIMI Frame Count (cTFC) and the Minimal Microcirculatory Resistance (MMR), as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter and thermodilution techniques, were compared after study interventions.

Results

Sixty-seven were included (30 allocated to pharmacologic and 37 to flow-mediated hyperemia). After study interventions, cTFC (40.2±23.1vs. 39.2±20.7; p=0.858) and MMR (753.6±661.5vs. 993.3±740.8 Wood units; p=0.174) were similar between groups. TIMI 3 flow was observed in 26.7%vs. 27.0% (p=0.899). Flow-mediated hyperemia showed two different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and non-fatal heart failure were observed in 10.4% and 26.9%, respectively.

Conclusions

Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in STEMI patients (NCT04685941).
Predicting elevated natriuretic peptide in chest radiography: Emerging utilization gap for artificial intelligence
Authors: Kagawa Eisuke , Kato Masaya , Oda Noboru , Kunita Eiji , Nagai Michiaki , Yamane Aya , Matsui Shogo , Yoshitomi Yuki , Shimajiri Hiroto , Hirokawa Tatsuya , Ishida Shunsuke , Kurimoto Genki , Dote Keigo
Published: February 2023

Aims

This study assessed an artificial intelligence (AI) model’s performance in predicting elevated brain natriuretic peptide (BNP) levels from chest radiograms and its effect on human diagnostic performance.

Methods and results

Patients who underwent chest radiography and BNP testing on the same day were included. Data were sourced from two hospitals: one for model development, and the other for external testing. Two final ensemble models were developed to predict elevated BNP levels of >= 200 pg/mL and >= 100 pg/mL, respectively. Humans were evaluated to predict elevated BNP levels, followed by the same test, referring to the AI model’s predictions. The 8390 images from 1334 patients were collected for model creation, and 1713 images from 273 patients for tests. The AI model achieved an accuracy of 0.855, precision of 0.873, sensitivity of 0.827, specificity of 0.882, f1 score of 0.850, and receiver-operating-characteristics area-under-curve of 0.929. The accuracy of the testing with the 100 images by 35 participants significantly improved from 0.708±0.049 to 0.829±0.069 (P < 0.001) with the AI assistance (an accuracy of 0.920). Without the AI assistance, the accuracy of the experts was higher than that of non-experts (0.728±0.051 vs. 0.692±0.042, P = 0.030); however, with the AI assistance, the accuracy of the non-experts was rather higher than that of the experts (0.851±0.074 vs. 0.803±0.054, P = 0.033).

Conclusion

The AI model can predict elevated BNP levels from chest radiograms and has the potential to improve human performance. The gap in utilizing new tools represents one of the emerging issues.

Graphical Abstract

We developed AI models using an ensemble method to predict elevated BNP levels. The AI model achieved a higher accuracy rate than any individual participant. While the accuracy of experts was higher in the non-assisted test, with the AI assistance, the accuracy of non-experts surpassed that of the experts. AI, artificial intelligence; AUC, area-under-curve; BNP, brain natriuretic peptide; GPU, graphic processing unit; PR, precision-recall; ROC, receiver-operating-characteristics.
Towards the Genome-scale Discovery of Bivariate Monotonic Classifiers
Authors: Fourquet Océane , Krejca Martin S. , Doerr Carola , Schwikowski Benno
Published: February 2023

Motivation

Bivariate monotonic classifiers (BMCs) are based on pairs of input features. Like many other models used for machine learning, they can capture non-linear patterns in high-dimensional data. At the same time, they are simple and easy to interpret. Until now, the use of BMCs on a genome scale was hampered by the high computational complexity of the search for pairs of features with a high leave-one-out performance estimate.

Results

We introduce thefastBMCalgorithm, which drastically speeds up the identification of BMCs. The algorithm is based on a mathematical bound for the BMC performance estimate while maintaining optimality. We show empirically that fastBMC speeds up the computation by a factor of at least 15 already for a small number of features, compared to the traditional approach. For two of the three clinical datasets that we consider here, the resulting possibility of considering much larger sets of features translates into significantly improved classification performance. As an example for the high degree of interpretability of BMCs, we discuss a straightforward interpretation of a BMC glioblastoma survival predictor, an immediate novel biomedical hypothesis, options for biomedical validation, and treatment implications.

Conclusions

fastBMC enables the rapid construction of robust and interpretable ensemble models using BMC, facilitating the discovery of interesting gene pairs and their contributions to the underlying biology.

Availability

We provide the first open-source implementation for learning BMCs, and an implementation of fastBMC in particular, all in Python, athttps://github.com/oceanefrqt/fastBMC.
Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer
Authors: García-Martínez José Manuel , Chocarro-Calvo Ana , Martínez-Useros Javier , Fernández-Aceñero María Jesús , Fiuza M. Carmen , Cáceres-Rentero Jose , De la Vieja Antonio , Barbáchano Antonio , Muñoz Alberto , Larriba María Jesús , García-Jiménez Custodia
Published: February 2023

Posttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD+-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D3(1,25(OH)2D3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)2D3. This effect is reproduced by the SIRT1 activator SRT1720, suggesting that SIRT1 activators may offer new therapeutic possibilities for colon cancer patients who are VD deficient or unresponsive. Moreover, this might be extrapolated to inflammation and other VD deficiency-associated and highly prevalent diseases in which SIRT1 plays a prominent role.
Synthetic lipid rafts formed by cholesterol nano-patch induce early T cell activation
Authors: Jung Yunmin , Kim Young-Joo , Noh Kunwoo , Lee Sunmi , Kwak Minsuk
Published: February 2023

Lipid rafts cluster at the immunological synapse during activation and serve as signaling hubs in T cells. While cholesterol plays a crucial role in lipid raft formation, the impact of their spatial configuration remains less understood. Here, we introduce programmable DNA origami, cholesterol nano-patch, for nanoscale spatial control of cholesterols on live T cell membranes, enabling us to elucidate their roles in lipid raft formation, receptor activation, and intracellular signaling. We demonstrate that CNPs with high-density cholesterol arrangements efficiently bind to the T cell plasma membrane and form a large and polarized coalescence, leading to the stabilization of ordered lipid membrane domains by increasing the local concentration of cholesterols. These synthetic lipid rafts colocalize with flotillin-1, a raft-associated protein, and promote the membrane reorganization and physical segregation of key signaling molecules, such as T cell receptors, Lck and LAT kinases, and CD45. Consequently, this leads to early T cell activation in the absence of antigenic stimulation. Our DNA origami approach demonstrates the direct role of cholesterol in lipid raft formation, leading to membrane phase separation and protein reorganization, which are sufficient to induce early T cell activation.
Lupus RGMX: Social and Clinical Characteristics and their Contribution to Quality of Life in a Mexican Cohort with SLE
Authors: Ana Laura Hernández-Ledesma , Domingo Martínez , Elizabeth Fajardo-Brigido , Román-López Talía V. , Karen Nuñez-Reza , Sandra Valentina Vera del Valle , Donaji Domínguez-Zúñiga , Lizbet Tinajero-Nieto , Angélica Peña-Ayala , Estefania Torres-Valdez , Gabriel Frontana-Vázquez , Maria Gutierrez-Arcelus , Florencia Rosetti , Sarael Alcauter , Rentería Miguel E. , Ruiz-Contreras Alejandra E. , Deshiré Alpízar-Rodríguez , Alejandra Medina-Rivera
Published: February 2023

BACKGROUND

Although higher prevalence, disease activity, damage accumulation and mortality of systemic lupus erythematosus (SLE) are observed among Latin American, North American admixed population, African descendants and Native Americans, the information about SLE in Latin American countries, such as Mexico, is scarce.

OBJECTIVES

To present Lupus RGMX, a multidisciplinary effort to generate a national digital patient registry to enrich the understanding of Mexican people with SLE.

METHODS

Mexican patients with SLE registered between May 2021 and January 2023 in Lupus RGMX were included. Sociodemographic, socioeconomic, and clinical characteristics, along with quality-of-life perception (QoL) were assessed using self-reported data. We compared the QoL obtained from patients with SLE with two groups of non-SLE Mexican subjects. Descriptive statistics, comparisons analyses and a multivariate nonparametric regression model were performed.

RESULTS

A total of 1172 of lupus patients were included; of which 93.9% were women. The mean age±SD was 36.6±10.7 years, with 37.1% of the individuals between 41 and 50 years. The 24.9% reported a calculated monthly income of 430 USD (8,612 MXN). Lower QoL scores were observed in the SLE group, especially in subjects with lower socioeconomic level. Health perception, QoL perception and socioeconomic status were the variables with greater importance to predict total WHOQoL scores.

CONCLUSION

The design and implementation of Lupus RGMX imply a pioneering approach to unraveling SLE in Mexicans. Further studies from Lupus RGMX will be focused on enriching the representation of the Mexican population and include other aspects that may allow us to improve our understanding of the disease in our population.