bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare ribosomal RNA sequences from archaea stabilize the bacterial ribosome
Authors: Nissley Amos J , Penev Petar I , Watson Zoe L , Banfield Jillian F , Cate Jamie H D
Published: January 2023

The ribosome serves as the universally conserved translator of the genetic code into proteins and supports life across diverse temperatures ranging from below freezing to above 120°C. Ribosomes are capable of functioning across this wide range of temperatures even though the catalytic site for peptide bond formation, the peptidyl transferase center, is nearly universally conserved. Here we find that Thermoproteota, a phylum of thermophilic Archaea, substitute cytidine for uridine at large subunit rRNA positions 2554 and 2555 (Escherichia coli numbering) in the A loop, immediately adjacent to the binding site for the 3′-end of A-site tRNA. We show by cryo-EM that E. coli ribosomes with uridine to cytidine mutations at these positions retain the proper fold and post-transcriptional modification of the A loop. Additionally, these mutations do not affect cellular growth, protect the large ribosomal subunit from thermal denaturation, and increase the mutational robustness of nucleotides in the peptidyl transferase center. This work identifies sequence variation across archaeal ribosomes in the peptidyl transferase center that likely confers stabilization of the ribosome at high temperatures and develops a stable mutant bacterial ribosome that can act as a scaffold for future ribosome engineering efforts.
Cold-induced inhibition of photosynthesis-related genes integrated by a TOP6 complex in rice mesophyll cells
Authors: Xu Zhan , Zhang Jianxiang , Wang Xu , Essemine Jemaa , Jin Jing , Qu Mingnan , Xiang Yong , Chen Weixiong
Published: January 2023

Photosynthesis is the most temperature-sensitive process in the plant kingdom, but how the photosynthetic pathway responds during low-temperature exposure remains unclear. Herein, cold stress (4°C) induced widespread damage in the form DNA double-stranded breaks (DSBs) in the mesophyll cells of rice (Oryza sativa), subsequently causing a global inhibition of photosynthetic carbon metabolism (PCM) gene expression. Topoisomerase genes TOP6A3 and TOP6B were induced at 4°C and their encoded proteins formed a complex in the nucleus. TOP6A3 directly interacted with KU70 to inhibit its binding to cold-induced DSBs, which was facilitated by TOP6B, finally blocking the loading of LIG4, a component of the classic non-homologous end joining (c-NHEJ) pathway. The repression of c-NHEJ repair imposed by cold extended DSB damage signaling, thus prolonging the inhibition of photosynthesis in leaves. Furthermore, the TOP6 complex negatively regulated 13 crucial PCM genes by directly binding to their proximal promoter regions. Phenotypically, TOP6A3 overexpression exacerbated the γ-irradiation-triggered suppression of PCM genes and led to the hypersensitivity of photosynthesis parameters to cold stress, dependent on the DSB signal transducer ATM. Globally, the TOP6 complex acts as a signal integrator to control PCM gene expression and synchronize cold-induced photosynthesis inhibition, which modulates carbon assimilation rates immediately in response to changes in ambient temperature.
Impact of different immunosuppressive protocols on clinical outcomes in obese kidney transplant recipients: a propensity score–matched analysis
Authors: Serna-Higuita Lina Maria , Della Penna Andrea , Guthoff Martina , Heyne Nils , Beer-Hammer Sandra , Nadalin Silvio , Martus Peter , Königsrainer Alfred , Quante Markus
Published: January 2023

Background

Although obesity has become a significant problem in transplantation medicine, the impact of different immunosuppressive protocols on clinical outcomes in obese transplant recipients remains unclear.

Methods

We performed an analysis of the Scientific Registry of Transplant Recipients database. Kidney transplant recipients were categorized according to body mass index (BMI) categories and immunosuppressive protocols: (i) tacrolimus/mycophenolate mofetil (Tac-MMF), (ii) mTOR-inhibitor/Tac (mTORi-Tac), (iii) mTORi/cyclosporin (mTORi-Cyc) and (iv) mTORi-MMF.

Results

Graft recipients with advanced obesity (BMI ≥35 kg/m2) exhibited significantly lower rates of acute rejection during the first year after transplantation in the mTORi-Tac (6.4%) group compared with Tac-MMF (11.2%). Obesity class 1 (30 < BMI < 35 kg/m2) was associated with a significant risk of acute rejection for the mTORi-Tac group [obesity class 1 hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.21–2.62, P = .003]. A similar trend was observed in the Tac-MMF group for advanced obesity HR 1.29; 95% CI 0.96–1.73, P = .087). For the Tac-MMF group, recipients with both overweight and obesity had significantly impaired survival due to cardiovascular events and also increased mortality due to infection in advanced obesity. Combination of mTORi and calcineurin inhibitor was associated with lower rejection rates and stable long-term kidney function while reducing cardiovascular side effects linked to calcineurin inhibitors in obese kidney graft recipients.

Conclusion

These results are critical for the growing number of obese graft recipients and warrant prospective evaluation.
Mapping the signaling network of BIN2 kinase using TurboID-mediated biotin labeling and phosphoproteomics
Authors: Kim Tae-Wuk , Park Chan Ho , Hsu Chuan-Chih , Kim Yeong-Woo , Ko Yeong-Woo , Zhang Zhenzhen , Zhu Jia-Ying , Hsiao Yu-Chun , Branon Tess , Kaasik Krista , Saldivar Evan , Li Kevin , Pasha Asher , Provart Nicholas J , Burlingame Alma L , Xu Shou-Ling , Ting Alice Y , Wang Zhi-Yong
Published: January 2023

Elucidating enzyme–substrate relationships in posttranslational modification (PTM) networks is crucial for understanding signal transduction pathways but is technically difficult because enzyme–substrate interactions tend to be transient. Here, we demonstrate that TurboID-based proximity labeling (TbPL) effectively and specifically captures the substrates of kinases and phosphatases. TbPL-mass spectrometry (TbPL-MS) identified over 400 proximal proteins of Arabidopsis thaliana BRASSINOSTEROID-INSENSITIVE2 (BIN2), a member of the GLYCOGEN SYNTHASE KINASE 3 (GSK3) family that integrates signaling pathways controlling diverse developmental and acclimation processes. A large portion of the BIN2-proximal proteins showed BIN2-dependent phosphorylation in vivo or in vitro, suggesting that these are BIN2 substrates. Protein–protein interaction network analysis showed that the BIN2-proximal proteins include interactors of BIN2 substrates, revealing a high level of interactions among the BIN2-proximal proteins. Our proteomic analysis establishes the BIN2 signaling network and uncovers BIN2 functions in regulating key cellular processes such as transcription, RNA processing, translation initiation, vesicle trafficking, and cytoskeleton organization. We further discovered significant overlap between the GSK3 phosphorylome and the O-GlcNAcylome, suggesting an evolutionarily ancient relationship between GSK3 and the nutrient-sensing O-glycosylation pathway. Our work presents a powerful method for mapping PTM networks, a large dataset of GSK3 kinase substrates, and important insights into the signaling network that controls key cellular functions underlying plant growth and acclimation.
BASIC PENTACYSTEINE2 fine-tunes corm dormancy release inGladiolus
Authors: Li Jingru , Pan Wenqiang , Liang Jiahui , Liu Chang , Li Danqing , Yang Yingdong , Qu Lianwei , Gazzarrini Sonia , Yi Mingfang , Wu Jian
Published: January 2023

Bud dormancy is an important trait in geophytes that largely affects their flowering process and vegetative growth after dormancy release. Compared with seed dormancy, the regulation of bud dormancy is still largely unclear. Abscisic acid (ABA) acts as the predominant hormone that regulates the whole dormancy process. In Gladiolus (Gladiolus hybridus), cold storage promotes corm dormancy release (CDR) by repressing ABA biosynthesis and signaling. However, the mechanisms governing ABA-related processes during CDR via epigenetics are poorly understood. Here, we show that class I BASIC PENTACYSTEINE2, (GhBPC2) directly binds to 9-CIS-EPOXYCAROTENOID DIOXYGENASE (GhNCED) and ABA INSENSITIVE5 (GhABI5) loci and down-regulates their expression to accelerate CDR. During CDR, histone modifications change dramatically at the GhBPC2-binding loci of GhABI5 with an increase in H3K27me3 and a decrease in H3K4me3. GhBPC2 is involved in both H3K27me3 and H3K4me3 and fine-tunes GhABI5 expression by recruiting polycomb repressive complex 2 (PRC2) and the chromatin remodeling factor EARLY BOLTING IN SHORT DAYS (GhEBS). These results show GhBPC2 epigenetically regulates CDR in Gladiolus by mediating GhABI5 expression with PRC2 and GhEBS.
RORγt inhibition ameliorates IL-23 driven experimental psoriatic arthritis by predominantly modulating γδ-T cells
Authors: Mortier Céline , Gracey Eric , Coudenys Julie , Manuello Teddy , Decruy Tine , Maelegheer Margaux , Stappers Flore , Gilis Elisabeth , Gaublomme Djoere , Van Hoorebeke Luc , Van Welden Sophie , Ambler Catherine , Hegen Martin , Symanowicz Peter , Steyn Stefan , Berstein Gabriel , Elewaut Dirk , Venken Koen
Published: January 2023

Objective

Divergent therapeutic outcomes on different disease domains have been noted with IL-23 and IL-17A-blockade in PsA. Therefore, elucidating the role of RORγt, the master regulator of type 17 immune responses, is of potential therapeutic interest. To this end, RORγt inhibition was assessed in combined skin, joint and gut inflammation in vivo, using a PsA model.

Methods

We tested the efficacy of a RORγt antagonist in B10.RIII mice challenged with systemic overexpression of IL-23 by hydrodynamic injection of IL-23 enhanced episomal vector (IL-23 EEV). Clinical outcomes were evaluated by histopathology. Bone density and surface erosions were examined using micro-computed tomography. Cytokine production was measured in serum and by intracellular flow cytometry. Gene expression in PsA-related tissues was analysed by qPCR.

Results

RORγt-blockade significantly ameliorated psoriasis, peripheral arthritis and colitis development in IL-23 EEV mice (improvement of clinical scores and weight loss respectively by 91.8%, 58.2% and 7.0%, P < 0.001), in line with profound suppression of an enhanced type IL-17 immune signature in PsA-affected tissues. Moreover, inflammation-induced bone loss and bone erosions were reduced (P < 0.05 in calcaneus, P < 0.01 in tibia). Sustained IL-23 overexpression resulted in only mild signs of sacroiliitis. Gamma-delta (γδ)-T cells, the dominant source of T cell-derived IL-17A and IL-22, were expanded during IL-23 overexpression, and together with Th17 cells, clearly countered by RORγt inhibition (P < 0.001).

Conclusion

RORγt-blockade shows therapeutic efficacy in a preclinical PsA model with protection towards extra-musculoskeletal manifestations, reflected by a clear attenuation of type 17 cytokine responses by γδ-T cells and Th17 cells.
A new entity in the NARS2 variant: the first reported case of type 1 diabetes mellitus associated with the phenotype
Authors: Cokyaman Turgay , Cetin Huriye , Dogan Durmus , Silan Fatma
Published: January 2023

NARS2 mutations are known to cause various clinical phenotypes such as nonsyndromic hearing loss, Leigh/Alpers syndrome, refractory epilepsy, developmental delay, intellectual disability and myopathy. We presented the first Turkish variant of NASR2 and added type 1 diabetes mellitus (DM), which was not previously described in the phenotype spectrum of this disease. A 4.5-month-old girl presented with hearing loss, hypotonia, refractory myoclonic epilepsy, severe developmental delay and large subdural hemorrhage. In the first year of the follow-up, type 1 DM developed. A homozygous missense mutation, [c.500 A>G, p.H167R] in the NARS2 gene was detected in the trio-based whole-exome sequencing (WES). In this disease, in addition to multi-organ involvement, type 1 DM may also develop, as in our case. Since it is a mitochondrial disease, the decision to treat with valproic acid should be reconsidered. The long diagnostic process can be shortened with WES.
Using Pressure Mapping to Compare Efficacy of Patient Bed Positioning Devices in Participants Who Are Able-Bodied and Those with Tetraplegia
Authors: Earnest Katherine , Zoellick Samantha
Published: January 2023

OBJECTIVE

To compare the effectiveness of four positioning aids in able-bodied participants and those with tetraplegia, to determine (1) if devices differed with regard to pressure reduction and (2) if results differed for able-bodied participants versus those with tetraplegia.

METHODS

Forty volunteers (20 able-bodied and 20 with tetraplegia) participated. The variable of interest was reduction in mean pressure in the sacral region, measured in mm Hg. Testing was conducted in a hospital bed using a tissue-interface pressure-mapping system. Four bed positioning devices were examined in use at both 0° and 30° head-of-bed elevations: standard hospital pillows, fluidized positioners, foam wedge positioners, and polystyrene bead wedge positioners.

RESULTS

No between-group differences were found for participant type (able-bodied vs tetraplegic). However, the positioning devices tested did differ significantly in pressure reduction. Foam wedge positioners, polystyrene bead wedge positioners, and fluidized positioners all resulted in greater reduction in pressure over an area inclusive of the sacrum, ischia, and buttocks when compared with standard hospital pillows, with foam wedges performing best.

CONCLUSIONS

Better pressure reduction over the sacrum, buttocks, and ischia can be achieved when using devices specifically designed for patient positioning in bed as opposed to using standard hospital pillows. Data were not significantly different between able-bodied participants and participants with tetraplegia. Thus, pressure-mapping data examining the efficacy of bed-positioning devices using convenience sampling of able-bodied individuals can likely be generalized to apply to a population with tetraplegia as well.
New Injury Patterns in Pediatric Supracondylar Fractures During COVID-19: Beds Are the New Monkey Bars
Authors: Soriano Kylen K.J. , Sabatini Coleen S. , Brar Ravinder K. , Jagodzinski Jason E. , Livingston Kristin S.
Published: January 2023

Background:

The coronavirus disease 2019 (COVID-19) pandemic drastically altered children’s activity patterns. Our goal was to investigate how COVID-19 affected demographics, injury characteristics, treatment patterns, follow-up, and outcomes in pediatric supracondylar humerus (SCH) fractures.

Methods:

This was an Institutional Review Board–approved retrospective analysis of patients undergoing surgery for a SCH fracture from May to November 2019 (pre-COVID-19) and from May to November 2020 (during COVID-19) at 2 tertiary children’s hospitals. Demographic information, injury characteristics, hospital course, and follow-up data were collected and compared.

Results:

SCH fractures decreased by >50% from 2019 (149) to 2020 (72). Children in the 2020 cohort were younger (mean 5.2 y old) compared with 2019 (6.0 y old) (P=0.019). Mechanism of injury was significantly different in 2020 (P<0.001), as the proportion of trampoline and furniture fractures increased from 8% and 17% to 15% and 33%, respectively. The proportion of playground and monkey bar fractures decreased from 20% and 17% to 3% and 4%, respectively. Distribution of Gartland type and neurovascular injury rates were similar in 2019 and 2020 (P=0.411 and 0.538). Time from emergency department admission to the operating room and duration of hospital admission were both unchanged from 2019 to 2020 (P=0.864 and 0.363). The duration of postoperative follow-up in 2019 was 94.5 days compared with 72.8 days in 2020 (P=0.122), as more pandemic patients were lost to follow up (22.5% vs. 35.2%,P=0.049).

Conclusions:

The demographics, mechanism of injury, and follow-up practices of pediatric SCH fractures changed significantly during the pandemic, likely because of school closures and lock-downs changing activity patterns. Different mechanisms of injury affected younger patients and reflected the new ways children played. Trampoline-related and furniture-related injuries overtook the classic playground falls as primary mechanism of injury. Despite the need for COVID-19 testing, there was no delay in time to the operating room. Hospitalization duration did not change, yet postoperative follow-up was shorter, and more patients were lost to follow up. Despite these stressors, outcomes remained excellent in most children.

Level of Evidence:

Level III—Retrospective comparative study.
Overt and Occult Hypoxemia in Patients Hospitalized With COVID-19
Authors: Gadrey Shrirang M. , Mohanty Piyus , Haughey Sean P. , Jacobsen Beck A. , Dubester Kira J. , Webb Katherine M. , Kowalski Rebecca L. , Dreicer Jessica J. , Andris Robert T. , Clark Matthew T. , Moore Christopher C. , Holder Andre , Kamaleswaran Rishi , Ratcliffe Sarah J. , Moorman J. Randall
Published: January 2023

IMPORTANCE:

Progressive hypoxemia is the predominant mode of deterioration in COVID-19. Among hypoxemia measures, the ratio of the Pao
2 to the Fio
2 (P/F ratio) has optimal construct validity but poor availability because it requires arterial blood sampling. Pulse oximetry reports oxygenation continuously (ratio of the Spo
2 to the Fio
2 [S/F ratio]), but it is affected by skin color and occult hypoxemia can occur in Black patients. Oxygen dissociation curves allow noninvasive estimation of P/F ratios (ePFRs) but remain unproven.

OBJECTIVES:

Measure overt and occult hypoxemia using ePFR.

DESIGN, SETTING, AND PARTICIPANTS:

We retrospectively studied COVID-19 hospital encounters (n = 5,319) at two academic centers (University of Virginia [UVA] and Emory University).

MAIN OUTCOMES AND MEASURES:

We measured primary outcomes (death or ICU transfer within 24 hr), ePFR, conventional hypoxemia measures, baseline predictors (age, sex, race, comorbidity), and acute predictors (National Early Warning Score [NEWS] and Sequential Organ Failure Assessment [SOFA]). We updated predictors every 15 minutes. We assessed predictive validity using adjusted odds ratios (AORs) and area under the receiver operating characteristic curves (AUROCs). We quantified disparities (Black vs non-Black) in empirical cumulative distributions using the Kolmogorov-Smirnov (K-S) two-sample test.

RESULTS:

Overt hypoxemia (low ePFR) predicted bad outcomes (AOR for a 100-point ePFR drop: 2.7 [UVA]; 1.7 [Emory]; p < 0.01) with better discrimination (AUROC: 0.76 [UVA]; 0.71 [Emory]) than NEWS (0.70 [both sites]) or SOFA (0.68 [UVA]; 0.65 [Emory]) and similar to S/F ratio (0.76 [UVA]; 0.70 [Emory]). We found racial differences consistent with occult hypoxemia. Black patients had better apparent oxygenation (K-S distance: 0.17 [both sites]; p < 0.01) but, for comparable ePFRs, worse outcomes than other patients (AOR: 2.2 [UVA]; 1.2 [Emory]; p < 0.01).

CONCLUSIONS AND RELEVANCE:

The ePFR was a valid measure of overt hypoxemia. In COVID-19, it may outperform multi-organ dysfunction models. By accounting for biased oximetry as well as clinicians’ real-time responses to it (supplemental oxygen adjustment), ePFRs may reveal racial disparities attributable to occult hypoxemia.
Surgical Science and the Evolution of Critical Care Medicine
Authors: Ferrada Paula , Cannon Jeremy W. , Kozar Rosemary A. , Bulger Eileen M. , Sugrue Michael , Napolitano Lena M. , Tisherman Samuel A. , Coopersmith Craig M. , Efron Phil A. , Dries David J. , Dunn Ty B. , Kaplan Lewis J.
Published: January 2023

Surgical science has driven innovation and inquiry across adult and pediatric disciplines that provide critical care regardless of location. Surgically originated but broadly applicable knowledge has been globally shared within the pagesCritical Care Medicineover the last 50 years.
Association Between Unmet Nonmedication Needs After Hospital Discharge and Readmission or Death Among Acute Respiratory Failure Survivors: A Multicenter Prospective Cohort Study*
Authors: Bose Somnath , Groat Danielle , Dinglas Victor D. , Akhlaghi Narjes , Banner-Goodspeed Valerie , Beesley Sarah J. , Greene Tom , Hopkins Ramona O. , Mir-Kasimov Mustafa , Sevin Carla M. , Turnbull Alison E. , Jackson James C. , Needham Dale M. , Brown Samuel M. ,   for the Addressing Post-Intensive Care Syndrome (APICS-01) Study Team
Published: January 2023

OBJECTIVES:

To characterize early unmet nonmedication discharge needs (UDNs), classified as durable medical equipment (DME), home health services (HHS), and follow-up medical appointments (FUAs) and explore their association with 90-day readmission and mortality among survivors of acute respiratory failure (ARF) who were discharged home.

DESIGN:

Prospective multicenter cohort study.

SETTING:

Six academic medical centers across United States.

PARTICIPANTS:

Adult survivors of ARF who required an ICU stay and were discharged home from hospital.

INTERVENTIONS:

None. Exposure of interest was the proportion of UDN for the following categories: DME, HHS, and FUA ascertained within 7–28 days after hospital discharge.

MEASUREMENTS AND MAIN RESULTS:

Two hundred eligible patients were recruited between January 2019 and August 2020. One-hundred ninety-five patients were included in the analytic cohort: 118 were prescribed DME, 134 were prescribed HHS, and 189 needed at least one FUA according to discharge plans. 98.4% (192/195) had at least one identified nonmedication need at hospital discharge. Median (interquartile range) proportion of unmet needs across three categories were 0 (0–15%) for DME, 0 (0–50%) for HHS, and 0 (0–25%) for FUA, and overall was 0 (0–20%). Fifty-six patients (29%) had 90-day death or readmission. After adjusting for prespecified covariates, having greater than the median level of unmet needs was not associated with an increased risk of readmission or death within 90 days of discharge (risk ratio, 0.89; 0.51–1.57; p = 0.690). Age, hospital length of stay, Acute Physiology and Chronic Health Evaluation II severity of illness score, and Multidimensional Scale Perceived Social Support score were associated with UDN.

CONCLUSIONS:

UDN were common among survivors of ARF but not significantly associated a composite outcome of 90-day readmission or death. Our results highlight the substantial magnitude of UDN and identifies areas especially vulnerable to lapses in healthcare coordination.
Orbital Involvement in Multiple Myeloma
Authors: Shoji Marissa K. , Chen Ying , Topilow Nicole J. , Abou Khzam Rayan , Dubovy Sander R. , Johnson Thomas E.
Published: January 2023

Purpose:

To characterize clinical and radiographic features, management, and outcomes of patients with orbital involvement of multiple myeloma (MM).

Methods:

A retrospective chart review identified patients with MM and orbital involvement confirmed by histopathology at a single institution between 1995 and 2021. A comprehensive literature review was performed via PubMed to identify all previously reported cases of orbital MM.

Results:

Retrospective review identified 7 patients (43% male, mean age 68.7 years). Presenting symptoms included proptosis and diplopia. Orbital lesions were primarily located laterally (42.8%) with associated extraocular muscle (57.1%) or lacrimal gland (42.9%) involvement. Five patients (71.4%) had a previous diagnosis of systemic MM. Six patients received chemoradiation (85.7%). All patients had improvement of orbital disease with 2 patients deceased due to disease at follow-up (mean 8.9 months). Literature review identified 111 cases (46.8% male, mean age 58.6 years). 48.6% presented with orbital disease as the first manifestation of systemic MM. Lesions were most commonly located superolaterally (20.2%) with extraocular muscle infiltration (25.2%), lacrimal gland involvement (7.2%), and orbital bony destruction (39.6%). Treatments included chemoradiation, chemotherapy, or radiation alone. Approximately half (51.4%) of patients experienced improvement in orbital disease following treatment, and 48.6% were deceased at follow-up (mean 20.1 months).

Conclusions:

This study provides a new retrospective study and updated comprehensive literature review regarding orbital MM. Given its poor prognosis, characterization of orbital MM is essential for early diagnosis. Orbital MM is often unilateral, located superolaterally, and may represent the first manifestation of systemic disease. Treatment includes chemotherapy and radiation, which may improve orbital disease; however, the overall prognosis remains poor.
An audit of hysterectomy in a teaching hospital in India: Story of a decade
Authors: Pandey Deeksha , Hebbar Shripad , Reddy Inukollu Pranadeep , Lobo Viwal Venisa , Bansal Suvrati , Solipuram Divya , Suhas Nagashree , Habibullah Sarah Arsalan , Popat Rishi Jitesh , Agrawal Akshita , MG Sayyad
Published: January 2023

Background:

The appropriateness of hysterectomy has gained an interest in scrutiny and debate. Periodic audits of the prevailing clinical practices are imperative for insight, and to formulate recommendations and guidelines. We report the temporal trends of hysterectomies, over the last 10 years in a teaching hospital.

Methods:

Present study involved all patients who underwent hysterectomy at a teaching hospital, from January 1, 2012 to December 31, 2021. Patients were identified by medical record tracking using International Classification of Diseases-9 codes. Case records were reviewed for demography, indication for surgery, approach, complications, hospital stay, and histopathological correlation.

Results:

Over the years the absolute number of hysterectomies in our hospital has ranged from 414 to 597 (mean 476), barring the coronavirus 19 pandemic year. The proportion of hysterectomy among all gynaecological admissions has ranged from 6% to 9%, except in 2020 where this proportion dropped down to 4%. The indications, age distribution, surgical approach, and complications have remained almost same.

Conclusion:

We report a static trend in hysterectomy over the past 10 years. This audit provides an insight for the need of shifting the abdominal to vaginal route, in carefully chosen patients. This will be beneficial for the patients, and for the trainees, where they can learn under supervision. Availability and patient education about the nonsurgical management options for benign gynecological conditions, as well as awareness about sequelae of hysterectomy, will bring down the rate in countries such as India.
Update on classification of oncocytic neoplasms of the kidney
Authors: Oszwald André , Wasinger Gabriel , Zisser Lucia , Compérat Eva
Published: January 2023

Purpose of review

This review provides a summary of recent developments in classification of renal oncocytic neoplasms that were incorporated in the fifth edition WHO classification of renal tumors, released in 2022.

Recent findings

Besides the distinct entities of renal oncocytoma and chromophobe renal cell carcinoma, the WHO now acknowledges a heterogeneous group of oncocytic tumors of the kidney that can be reported as ‘oncocytic renal neoplasms of low malignant potential’. Case series by multiple institutions have revealed recurrent patterns of morphological features, protein marker expression, and genetic alterations within these neoplasms that may permit further subclassification in the future.

The new classification system provides pathologists with the opportunity to simplify the diagnostic workup and reporting of morphologically equivocal oncocytic neoplasms.
Defining Pediatric Chronic Critical Illness: A Scoping Review*
Authors: Zorko David J. , McNally James Dayre , Rochwerg Bram , Pinto Neethi , O’Hearn Katie , Almazyad Mohammed A. , Ames Stefanie G. , Brooke Peter , Cayouette Florence , Chow Cristelle , Junior José Colleti , Francoeur Conall , Heneghan Julia A. , Kazzaz Yasser M. , Killien Elizabeth Y. , Jayawarden Supun Kotteduwa , Lasso Ruben , Lee Laurie A. , O’Mahony Aoife , Perry Mallory A. , Rodríguez-Rubio Miguel , Sandarage Ryan , Smith Hazel A. , Welten Alexandra , Yee Belinda , Choong Karen ,   on behalf of the International Pediatric Chronic Critical Illness Collaborative
Published: January 2023

OBJECTIVES:

Children with chronic critical illness (CCI) are hypothesized to be a high-risk patient population with persistent multiple organ dysfunction and functional morbidities resulting in recurrent or prolonged critical care; however, it is unclear how CCI should be defined. The aim of this scoping review was to evaluate the existing literature for case definitions of pediatric CCI and case definitions of prolonged PICU admission and to explore the methodologies used to derive these definitions.

DATA SOURCES:

Four electronic databases (Ovid Medline, Embase, CINAHL, and Web of Science) from inception to March 3, 2021.

STUDY SELECTION:

We included studies that provided a specific case definition for CCI or prolonged PICU admission. Crowdsourcing was used to screen citations independently and in duplicate. A machine-learning algorithm was developed and validated using 6,284 citations assessed in duplicate by trained crowd reviewers. A hybrid of crowdsourcing and machine-learning methods was used to complete the remaining citation screening.

DATA EXTRACTION:

We extracted details of case definitions, study demographics, participant characteristics, and outcomes assessed.

DATA SYNTHESIS:

Sixty-seven studies were included. Twelve studies (18%) provided a definition for CCI that included concepts of PICU length of stay (n = 12), medical complexity or chronic conditions (n = 9), recurrent admissions (n = 9), technology dependence (n = 5), and uncertain prognosis (n = 1). Definitions were commonly referenced from another source (n = 6) or opinion-based (n = 5). The remaining 55 studies (82%) provided a definition for prolonged PICU admission, most frequently greater than or equal to 14 (n = 11) or greater than or equal to 28 days (n = 10). Most of these definitions were derived by investigator opinion (n = 24) or statistical method (n = 18).

CONCLUSIONS:

Pediatric CCI has been variably defined with regard to the concepts of patient complexity and chronicity of critical illness. A consensus definition is needed to advance this emerging and important area of pediatric critical care research.
The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease: A Secondary Analysis of the Age of Blood in Children in the PICU Trial*
Authors: Steffen Katherine M. , Tucci Marisa , Doctor Allan , Reeder Ron , Caro J. Jaime , Muszynski Jennifer A. , Spinella Philip C. ,   Pediatric Critical Care Blood Research Network (BloodNet) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

Guidelines recommend against RBC transfusion in hemodynamically stable (HDS) children without cardiac disease, if hemoglobin is greater than or equal to 7 g/dL. We sought to assess the clinical and economic impact of compliance with RBC transfusion guidelines.

DESIGN:

A nonprespecified secondary analysis of noncardiac, HDS patients in the randomized trial Age of Blood in Children (NCT01977547) in PICUs. Costs analyzed included ICU stay and physician fees. Stabilized inverse propensity for treatment weighting was used to create a cohort balanced with respect to potential confounding variables. Weighted regression models were fit to evaluate outcomes based on guideline compliance.

SETTING:

Fifty international tertiary care centers.

PATIENTS:

Critically ill children 3 days to 16 years old transfused RBCs at less than or equal to 7 days of ICU admission. Six-hundred eighty-seven subjects who met eligibility criteria were included in the analysis.

INTERVENTIONS:

Initial RBC transfusions administered when hemoglobin was less than 7 g/dL were considered “compliant” or “non-compliant” if hemoglobin was greater than or equal to 7 g/dL.

MEASUREMENTS AND MAIN RESULTS:

Frequency of new or progressive multiple organ system dysfunction (NPMODS), ICU survival, and associated costs. The hypothesis was formulated after data collection but exposure groups were masked until completion of planned analyses. Forty-nine percent of patients (338/687) received a noncompliant initial transfusion. Weighted cohorts were balanced with respect to confounding variables (absolute standardized differences < 0.1). No differences were noted in NPMODS frequency (relative risk, 0.86; 95% CI, 0.61–1.22; p = 0.4). Patients receiving compliant transfusions had more ICU-free days (mean difference, 1.73; 95% CI, 0.57–2.88; p = 0.003). Compliance reduced mean costs in ICU by $38,845 U.S. dollars per patient (95% CI, $65,048–$12,641).

CONCLUSIONS:

Deferring transfusion until hemoglobin is less than 7 g/dL is not associated with increased organ dysfunction in this population but is independently associated with increased likelihood of live ICU discharge and lower ICU costs.
Leveraging Clinical Informatics and Data Science to Improve Care and Facilitate Research in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Sanchez-Pinto L. Nelson , Sauthier Michaël , Rajapreyar Prakadeshwari , Brunow de Carvalho Werther , Jouvet Philippe , Newth Christopher ,   on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

The use of electronic algorithms, clinical decision support systems, and other clinical informatics interventions is increasing in critical care. Pediatric acute respiratory distress syndrome (PARDS) is a complex, dynamic condition associated with large amounts of clinical data and frequent decisions at the bedside. Novel data-driven technologies that can help screen, prompt, and support clinician decision-making could have a significant impact on patient outcomes. We sought to identify and summarize relevant evidence related to clinical informatics interventions in both PARDS and adult respiratory distress syndrome (ARDS), for the second Pediatric Acute Lung Injury Consensus Conference.

DATA SOURCES:

MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).

STUDY SELECTION:

We included studies of pediatric or adult critically ill patients with or at risk of ARDS that examined automated screening tools, electronic algorithms, or clinical decision support systems.

DATA EXTRACTION:

Title/abstract review, full text review, and data extraction using a standardized data extraction form.

DATA SYNTHESIS:

The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-six studies were identified for full text extraction to address the Patient/Intervention/Comparator/Outcome questions, and 14 were used for the recommendations/statements. Two clinical recommendations were generated, related to the use of electronic screening tools and automated monitoring of compliance with best practice guidelines. Two research statements were generated, related to the development of multicenter data collaborations and the design of generalizable algorithms and electronic tools. One policy statement was generated, related to the provision of material and human resources by healthcare organizations to empower clinicians to develop clinical informatics interventions to improve the care of patients with PARDS.

CONCLUSIONS:

We present two clinical recommendations and three statements (two research one policy) for the use of electronic algorithms and clinical informatics tools for patients with PARDS based on a systematic review of the literature and expert consensus.
Definition, Incidence, and Epidemiology of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Yehya Nadir , Smith Lincoln , Thomas Neal J. , Steffen Katherine M. , Zimmerman Jerry , Lee Jan Hau , Erickson Simon J. , Shein Steven L. ,   for the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

In 2015, the Pediatric Acute Lung Injury Consensus Conference (PALICC) provided the first pediatric-specific definitions for acute respiratory distress syndrome (pediatric acute respiratory distress syndrome [PARDS]). These definitions have since been operationalized in cohort and interventional PARDS studies. As substantial data have accrued since 2015, we have an opportunity to assess the construct validity and utility of the initial PALICC definitions. Therefore, the Second PALICC (PALICC-2) brought together multiple PARDS experts and aimed to identify and summarize relevant evidence related to the definition and epidemiology of PARDS and create modifications to the definition of PARDS.

DATA SOURCES:

MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).

STUDY SELECTION:

We included studies of subjects with PARDS, or at risk for PARDS, excluding studies pertaining primarily to adults except as specified for identifying age-specific cutoffs.

DATA EXTRACTION:

Title/abstract review, full-text review, and data extraction using a standardized data collection form.

DATA SYNTHESIS:

The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. A total of 97 studies were identified for full-text extraction addressing distinct aspects of the PARDS definition, including age, timing, imaging, oxygenation, modes of respiratory support, and specific coexisting conditions. Data were assessed in a Patient/Intervention/Comparator/Outcome format when possible, and formally summarized for effect size, risk, benefit, feasibility of implementation, and equity. A total of 17 consensus-based definition statements were made that update the definition of PARDS, as well as the related diagnoses of “Possible PARDS” and “At-Risk for PARDS.” These statements are presented alongside a summary of the relevant epidemiology.

CONCLUSIONS:

We present updated, data-informed consensus statements on the definition for PARDS and the related diagnoses of “Possible PARDS” and “At-Risk for PARDS.”
Noninvasive Respiratory Support for Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Carroll Christopher L. , Napolitano Natalie , Pons-Òdena Marti , Iyer Narayan Prabhu , Korang Steven Kwasi , Essouri Sandrine ,   on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

To develop evidence-based recommendations for the Second Pediatric Acute Lung Injury Consensus Conference (PALICC) regarding the effectiveness of noninvasive respiratory support for pediatric acute respiratory distress syndrome (PARDS). These include consideration of the timing and duration of noninvasive ventilation (NIV) and high-flow nasal cannula (HFNC), whether effectiveness varies by disease severity or by characteristics of treatment delivery, and best practices for the use of NIV.

DATA SOURCES:

MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).

STUDY SELECTION:

Searches included all studies involving the use of NIV or HFNC in children with PARDS or hypoxemic respiratory failure.

DATA EXTRACTION:

Title/abstract review, full-text review, and data extraction using a standardized data extraction form.

DATA SYNTHESIS:

The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Out of 6,336 studies, we identified 187 for full-text review. Four clinical recommendations were generated, related to indications, timing and duration of NIV in patients with PARDS, predictors of NIV failure and need for intubation (signs and symptoms of worsening disease including pulse oximetry saturation/Fio
2 ratio), and use of NIV in resource-limited settings. Six good practice statements were generated related to how and where to deliver NIV, the importance of trained experienced staff and monitoring, types of NIV interfaces, the use of sedation, and the potential complications of this therapy. One research statement was generated related to indications of HFNC in patients with PARDS.

CONCLUSIONS:

NIV is a widely used modality for the treatment of respiratory failure in children and may be beneficial in a subset of patients with PARDS. However, there needs to be close monitoring for worsening disease and NIV failure.
Diagnostic, Management, and Research Considerations for Pediatric Acute Respiratory Distress Syndrome in Resource-Limited Settings: From the Second Pediatric Acute Lung Injury Consensus Conference
Authors: Morrow Brenda M. , Agulnik Asya , Brunow de Carvalho Werther , Chisti Mohammod Jobayer , Lee Jan Hau ,   on behalf of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) Group of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2023

OBJECTIVES:

Diagnosis of pediatric acute respiratory distress syndrome (PARDS) in resource-limited settings (RLS) is challenging and remains poorly described. We conducted a review of the literature to optimize recognition of PARDS in RLS and to provide recommendations/statements for clinical practice and future research in these settings as part of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2).

DATA SOURCES:

MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).

STUDY SELECTION:

We included studies related to precipitating factors for PARDS, mechanical ventilation (MV), pulmonary and nonpulmonary ancillary treatments, and long-term outcomes in children who survive PARDS in RLS.

DATA EXTRACTION:

Title/abstract review, full-text review, and data extraction using a standardized data collection form.

DATA SYNTHESIS:

The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Seventy-seven studies were identified for full-text extraction. We were unable to identify any literature on which to base recommendations. We gained consensus on six clinical statements (good practice, definition, and policy) and five research statements. Clinicians should be aware of diseases and comorbidities, uncommon in most high-income settings, that predispose to the development of PARDS in RLS. Because of difficulties in recognizing PARDS and to avoid underdiagnosis, the PALICC-2 possible PARDS definition allows exclusion of imaging criteria when all other criteria are met, including noninvasive metrics of hypoxemia. The availability of MV support, regular MV training and education, as well as accessibility and costs of pulmonary and nonpulmonary ancillary therapies are other concerns related to management of PARDS in RLS. Data on long-term outcomes and feasibility of follow-up in PARDS survivors from RLS are also lacking.

CONCLUSIONS:

To date, PARDS remains poorly described in RLS. Clinicians working in these settings should be aware of common precipitating factors for PARDS in their patients. Future studies utilizing the PALICC-2 definitions are urgently needed to describe the epidemiology, management, and outcomes of PARDS in RLS.
Comparison of Physical Activity, Exercise Barriers, Physical Performance, and Fall Risks in Frail and Nonfrail Older Adults
Authors: Gözaçan Karabulut Demet , Sertel Meral , Tütün Yümin Eylem , Abit Kocaman Ayşe , Tarsuslu Tülay
Published: January 2023

Objectives:

The present research aimed to identify the difference between physical activity, physical performance, balance, fall risk, and exercise barriers in frail and nonfrail older adults.

Methods:

One hundred nineteen voluntary individuals older than 65 years and living in Kırıkkale were enrolled in the research. The Clinical Frailty Scale was employed to evaluate the frailty level of the individuals included in the study. In line with the data obtained after the evaluation, individuals were separated into 2 groups as frail and nonfrail individuals. Exercise barriers were evaluated with the Exercise Benefits/Barriers Scale (EBBS), physical activity level was evaluated with the Physical Activity Scale for the Elderly (PASE), lower extremity physical performance was assessed with the Short Physical Performance Battery (SPPB) test, and fall risk was assessed with the Self-Rated Fall Risk Questionnaire (FRQ).

Results:

Ninety-three of the individuals enrolled in the study were found to be nonfrail and 26 to be frail older adults. The mean age of the individuals in the nonfrail group was 70.36 ± 6.10 years, and the mean age of the individuals in the frail group was 76.53 ± 7.37 years. In the statistical analysis, the difference was revealed between the groups in terms of the exercise barriers subscore, EBBS total score, PASE leisure activity score, PASE total score, FRQ total score, and SPPB total result (P < .05). In the correlation analysis, there was a negative correlation between the frailty scale score and SPPB and a positive correlation between the frailty scale score and FRQ in nonfrail older adults (P < .05). However, there was a positive correlation between the frailty scale score and exercise barriers subscore, EBBS and FRQ total scores, and a negative correlation between the PASE leisure activities, work activities and PASE total score, and SPPB score in frail individuals (P < .05).

Conclusions:

Our results demonstrated that the physical activity levels of frail older adults were poorer, they had a higher fall risk, and their activity performance, including the lower extremity, was poorer than that of nonfrail older adults.
Secure Deep Learning on Genomics Data via a Homomorphic Encrypted Residue Activation Network
Authors: Song Chen , Shi Xinghua
Published: January 2023

Growing applications of deep learning on sensitive genomics and biomedical data introduce challenging privacy and secure problems. Homomorphic encryption (HE) is one of appropriate cryptographic techniques to provide secure machine learning evaluation by directly computing over encrypted data, so that allows the data owner and model owner to outsource processing of sensitive data to an untrusted server without leaking any information about the data. However, most current HE schemes only support limited arithmetic operations, which significantly hinder their applications to support secure deep learning algorithm. Considering the potential performance loss introduced for approximating activation function, in this paper, we develop a novel HE friendly deep network, named Residue Activation Network (ResActNet) to implement precise privacy-preserving machine learning algorithm with a non-approximating activation on HE scheme. We considered a residue activation strategy with a scaled power activation function in the deep network. In particular, a scaled power activation (SPA) function is set within the HE scheme, and so that can be directly deployed on HE computation. Moreover, we proposed a residue activation strategy to constrain the latent space in the training process for alleviating the optimization difficulty. We comprehensively evaluate ResActNet using diverse genomics datasets and widely-used image datasets. Our results demonstrate that ResActNet outperforms other alternative solutions to secure machine learning with HE and achieves low approximation errors in classification and regression tasks.