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In patients with a health care-associated infection (HAI), lengths of stay and costs increased >150% from 2019 to 2023, and were 2 to 6 times greater compared to concurrent non-HAI patients with the same diagnoses. Unlike surgical HAI, no device-associated HAI occurred before hospital day 12. These findings highlight the possibly under-recognized influence of delayed discharges on device-associated HAIs., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

As an alternative to target-driven drug discovery, phenotype-driven approaches identify compounds that counteract the overall disease effects by analyzing phenotypic signatures. Our study introduces a novel approach to this field, aiming to expand the search space for new therapeutic agents. We introduce PDGrapher, a causally-inspired graph neural network (GNN) designed to predict combinatorial perturbagens - sets of therapeutic targets - capable of reversing disease effects. Unlike methods that learn responses to perturbations, PDGrapher solves the inverse problem, which is to infer the perturbagens necessary to achieve a specific response - i.e., directly predicting perturbagens by learning which perturbations elicit a desired response. By encoding gene regulatory networks or protein-protein interactions, PDGrapher can predict unseen chemical or genetic perturbagens, aiding in the discovery of novel drugs or therapeutic targets. Experiments across nine cell lines with chemical perturbations show that PDGrapher successfully predicted effective perturbagens in up to 13.33% additional test samples and ranked therapeutic targets up to 35% higher than the competing methods, and the method shows competitive performance across ten genetic perturbation datasets. A key innovation of PDGrapher is its direct prediction capability, which contrasts with the indirect, computationally intensive models traditionally used in phenotype-driven drug discovery that only predict changes in phenotypes due to perturbations. The direct approach enables PDGrapher to train up to 25 times faster than methods like scGEN and CellOT, representing a considerable leap in efficiency. Our results suggest that PDGrapher can advance phenotype-driven drug discovery, offering a fast and comprehensive approach to identifying therapeutically useful perturbations., Competing Interests: Competing interests. G.G. is currently employed by Genentech, Inc. and F. Hoffmann-La Roche Ltd. I.H. is currently employed by Merck & Co., Inc.

Background: The dopaminergic agonist cabergoline (CAB) has been used in the pharmacological treatment of Cushing's disease (CD). The effect is attributed to the frequent expression of the dopamine receptor subtype 2 in corticotroph tumors. However, in-vivo studies have demonstrated the normalization of 24-h urinary cortisol (24-h UC) in approximately 30-40% of patients over the long term, mainly after surgical failure. The aim was to evaluate the effect of CAB as monotherapy in the early preoperative period and on the recurrence of CD., Methods: A single-center retrospective study was conducted in a tertiary referral center. Twenty-one patients with confirmed CD were included. The median age was 32 years (13-70), 86% were female, 10 had microadenomas, and 11 had macroadenomas. They were diagnosed from 1986 to 2016 and used CAB as monotherapy either in the preoperative period (N.=7, CABi) or upon recurrence before any other treatment (N.=14, CABr). A "complete response" was considered 24-h UC normalization and a "partial response" was considered a 24-h UC reduction of >50%. UC was obtained at the last follow-up evaluation. The normalization of late-night salivary cortisol (LNSC) after CAB use was evaluated in most patients, as well as the tumor diameter by pituitary MRI, before and after CAB treatment., Results: Complete response was achieved in 29% (6/21) of subjects after 14.9±16.4 months of treatment, with an average dose of 2.2±1.0 mg/week. Partial response occurred in 9.5% (2/21). LNSC normalized in 35% (6/17) of patients, and no variation in tumor diameter before and after CAB use was observed (N.=13): 6.8±6.8 vs. 7.2±7.1 mm. There was no normalization of 24-h-UC in the CABi subgroup at the end of the treatment, whereas 43% (6/14) of patients in the CABr subgroup reached complete response. The CABi subgroup was treated for 4.7±1.9 months, and the CABr subgroup was treated for 20.1±18.1 months. Both groups were administered similar doses of CAB (CABi 2.1±0.9 and CABr 2.3±1.1 mg/week). Interestingly, the difference between the subgroups' complete response was evident early on in the three months of treatment: no patients in the CABi subgroup vs. 6/10 (60%) in the CABr subgroup (P=0.035), despite a lower dose in the CABr subgroup (1.1 vs. 1.6; P=0.008). The normalization of LNSC occurred in 20% of the CABi subgroup and in 42% of the CABr subgroup., Conclusions: The normalization of 24-h UC and LNSC occurred in approximately 30% of all patients, mainly in those who used CAB for the recurrence of CD. Despite the small number of subjects in the CABi subgroup, the absence of hormone control in this subgroup discourages the use of this medication as primary therapy or as a preoperative treatment option.

Background: This study aimed to assess the medical costs, and the combined costs of fatal firearm injury and fatal falls during a 5 year period. While fatal firearm injury represents a significant public health concern, the healthcare community is faced with the significant challenge of fatal falls, particularly in light of the elderly population growth., Methods: Data were exported from the Web-based Injury Statistics Query and Reporting System database for fatal firearm and falls in patients aged between 15-85 years-old. The primary outcome was medical cost and the secondary outcome was combined costs (combination of medical costs and value of statistical life)., Results: The medical cost of fatal falls was significantly higher in 2015-2020 in all age groups. The combined cost was significantly higher in fatal firearm injury overall. We found the combined cost was higher in fatal falls after 2019 for patients in the 45-85+ age range. During 2015-2019, the percentage of fatal falls had a significant increase in all age ranges, with a rise in the slope in 2019 for patients over 65 years. The annual percent change (APC) for the proportion of fatal falls increased from 2015 to 2020, there was a significant increase in the slope after 2019 (2.81% APC before 2019 vs 6.95% after 2019)., Conclusion: Geriatric fatal falls have significantly higher medical costs compared with fatal firearm injury. The combined cost for fatal falls exceeded fatal firearm injury after 2019 which highlights the increasing socioeconomic burden of an aging population., Level of Evidence: Level III retrospective study., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The shock index (SI) is a known predictor of unfavorable outcomes in trauma. This study seeks to examine and compare the SI values between geriatric patients and younger adults., Methods: We conducted a retrospective study of the Trauma Quality Improvement Program database from 2017 to 2019. All patients≥ 25 y with injury severity score ≥ 16 were included. Age groups were defined as 25-44 y (group A), 45-64 y (group B), and ≥65 y (group C). SI was calculated for all patients. The primary outcome was mortality and secondary outcomes were need for blood transfusion and need for major surgical intervention (consisting angiography, exploratory laparotomy, and thoracotomy)., Results: A total of 244,943 patients were studied. The SI was highest in group A (0.82 ± 0.33) and lowest in group C (0.62 ± 0.30) (P < 0.001). Mortality rate of group C (17%) was significantly higher than group A (9.7%) and B (11.3%) (P < 0.001). In group A, each 0.1 increase in SI was associated with mortality (odds ratio [OR] = 1.079), need for blood transfusion (OR = 1.225) and need for major surgical intervention (OR = 1.347) (P < 0.001 for all). In group C, each 0.1 increase in SI was associated with mortality (OR = 1.126), need for blood transfusion (OR = 1.318), and need for major surgical intervention (OR = 1.648) (P < 0.001 for all). The area under the curve of SI was significantly higher in group C compared to other groups for needing a major surgical intervention and need for blood transfusion (P < 0.05 for both)., Conclusions: These results highlight the significance of the SI as a valuable indicator in geriatric patients with severe trauma. The findings show that SI predicts outcomes in geriatrics more strongly than in younger counterparts., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The health care system for the elderly is fragmented, that is worsened when readmission occurs to different hospitals. There is limited investigation into the impact of fragmentation on geriatric trauma patient outcomes. The aim of this study was to compare the outcomes following readmissions after geriatric trauma. The Nationwide Readmissions Database (2016-2017) was queried for elderly trauma patients (aged ≥65 years) readmitted due to any cause. Patients were divided into 2 groups according to readmission: index vs non-index hospital. Outcomes were 30 and 180-day complications, mortality, and the number of subsequent readmissions. Multivariable logistic regression was performed to analyze the independent predictors of fragmentation of care. A total of 36,176 trauma patients were readmitted, of which 3856 elderly patients (aged ≥65 years) were readmitted: index hospital (3420; 89%) vs non-index hospital (436; 11%). Following 1:2 propensity matching, elderly with non-index hospital readmission had higher rates of death and MI within 180 days ( P = .01 and .02, respectively). They had statistically higher 30 and 180-day pneumonia ( P < .01), CHF ( P < .01), arrhythmias ( P < .01), MI ( P < .01), sepsis ( P < .01), and UTI ( P < .01). On multivariable binary logistic regression analysis, pneumonia (OR 1.70, P = .03), congestive heart failure (CHF) (OR 1.80, P = .03), female gender (OR .72, P = .04), and severe Head and Neck trauma (AIS≥3) (OR 1.50, P < .01) on index admission were independent predictors of fragmentation of care. While the increase in time to readmission (OR 1.01, P < .01) was also associated independently with non-index hospital admission. Fragmented care after geriatric trauma could be associated with higher mortality and complications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy. Management of prolactinoma in special situations is discussed, including cystic lesions, mixed growth hormone-secreting and prolactin-secreting adenomas and giant and aggressive prolactinomas. Furthermore, considerations for pregnancy and fertility are outlined, as well as management of prolactinomas in children and adolescents, patients with an underlying psychiatric disorder, postmenopausal women, transgender individuals and patients with chronic kidney disease. The workshop concluded that, although treatment resistance is rare, there is a need for additional therapeutic options to address clinical challenges in treating these patients and a need to facilitate international registries to enable risk stratification and optimization of therapeutic strategies., (© 2023. Springer Nature Limited.)

The rapid progress in the field of deep learning has had a significant impact on protein design. Deep learning methods have recently produced a breakthrough in protein structure prediction, leading to the availability of high-quality models for millions of proteins. Along with novel architectures for generative modeling and sequence analysis, they have revolutionized the protein design field in the past few years remarkably by improving the accuracy and ability to identify novel protein sequences and structures. Deep neural networks can now learn and extract the fundamental features of protein structures, predict how they interact with other biomolecules, and have the potential to create new effective drugs for treating disease. As their applicability in protein design is rapidly growing, we review the recent developments and technology in deep learning methods and provide examples of their performance to generate novel functional proteins., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Nonoperative management (NOM) of acute calculous cholecystitis (ACC) in patients with cirrhosis was proposed. We examined the outcomes of cirrhotic patients with ACC treated with cholecystectomy compared to NOM., Methods: We analyzed the 2017-Nationwide Readmissions Database including cirrhotic patients with ACC. Patients were stratified: cholecystectomy, percutaneous cholecystostomy (PCT), and antibiotics only., Primary Outcomes: complications, failure of NOM., Secondary Outcomes: mortality, length of stay (LOS), and charges., Results: 3454 patients were identified. 1832 underwent cholecystectomy, 360 PCT, and 1262 were treated with antibiotics. PCT patients had higher mortality 16.9% vs. the antibiotics group 10.9% vs. cholecystectomy group 4.2%. PCT patients had longer LOS, but lower charges compared to the operative group. Failure of NOM was 28.2%. On regression, PCT was associated with mortality., Conclusion: ACC remains a morbid disease in cirrhosis patients. One in three failed NOM, had longer LOS, and higher mortality. Further studies are warranted to identify predictors of NOM failure., Level of Evidence: Level III, prognostic., Competing Interests: Declaration of competing interest There are no identifiable conflicts of interests to report. The authors have no financial or proprietary interest in the subject matter or materials discussed in the manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Radiotherapy response of rectal cancer patients is dependent on a myriad of molecular mechanisms including response to stress, cell death, and cell metabolism. Modulation of lipid metabolism emerges as a unique strategy to improve radiotherapy outcomes due to its accessibility by bioactive molecules within foods. Even though a few radioresponse modulators have been identified using experimental techniques, trying to experimentally identify all potential modulators is intractable. Here we introduce a machine learning (ML) approach to interrogate the space of bioactive molecules within food for potential modulators of radiotherapy response and provide phytochemically-enriched recipes that encapsulate the benefits of discovered radiotherapy modulators. Potential radioresponse modulators were identified using a genomic-driven network ML approach, metric learning and domain knowledge. Then, recipes from the Recipe1M database were optimized to provide ingredient substitutions maximizing the number of predicted modulators whilst preserving the recipe's culinary attributes. This work provides a pipeline for the design of genomic-driven nutritional interventions to improve outcomes of rectal cancer patients undergoing radiotherapy., (© 2023. Springer Nature Limited.)

BACKGROUND Genitofemoral neuralgia is a pain syndrome that involves injury to the genitofemoral nerve and is frequently iatrogenic. We report intraoperative nerve localization using ultrasound, nerve stimulation, and the cremasteric reflex in the surgical treatment of genitofemoral neuralgia. CASE REPORT A 49-year-old man with a history of extracorporeal membrane oxygenation with cannulation sites in bilateral inguinal regions presented with right groin numbness and pain following decannulation. His symptoms corresponded to the distribution of the genitofemoral nerve. He had a Tinel's sign over the midpoint of his inguinal incision. A nerve block resulted in temporary resolution of his symptoms. Due to the presence of a pacemaker, peripheral nerve neuromodulation was contraindicated. He underwent external neurolysis and neurectomy of the right genitofemoral nerve. Following direct stimulation and ultrasound for localization, the nerve was further localized intraoperatively using nerve stimulation with monitoring for the presence of the cremasteric reflex. At his 1-month postoperative visit, his right medial thigh pain had resolved and his right testicular pain 50% improved; his residual pain continued to improve at last evaluation 3 months after surgery. CONCLUSIONS We report the successful use of nerve stimulation and the cremasteric reflex to aid in identification of the genitofemoral nerve intraoperatively for the treatment of genitofemoral neuralgia.

New methods promise transformative insights and conservation benefits.

Physical interactions between proteins are essential for most biological processes governing life 1 . However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic and structural data increase. This knowledge gap has been a major obstacle for the comprehensive understanding of cellular protein-protein interaction networks and for the de novo design of protein binders that are crucial for synthetic biology and translational applications 2-9 . Here we use a geometric deep-learning framework operating on protein surfaces that generates fingerprints to describe geometric and chemical features that are critical to drive protein-protein interactions 10 . We hypothesized that these fingerprints capture the key aspects of molecular recognition that represent a new paradigm in the computational design of novel protein interactions. As a proof of principle, we computationally designed several de novo protein binders to engage four protein targets: SARS-CoV-2 spike, PD-1, PD-L1 and CTLA-4. Several designs were experimentally optimized, whereas others were generated purely in silico, reaching nanomolar affinity with structural and mutational characterization showing highly accurate predictions. Overall, our surface-centric approach captures the physical and chemical determinants of molecular recognition, enabling an approach for the de novo design of protein interactions and, more broadly, of artificial proteins with function., (© 2023. The Author(s).)

Reports of Candida auris infection in patients without epidemiologic links to prior outbreaks are scarce. We describe the genomic epidemiology of such a case in Western New York. Before emergence, the patient received >60 days of excess antibiotics. Candida auris was recovered on near-patient surfaces after enhanced terminal cleanings., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

During the coronavirus disease 2019 (COVID-19) pandemic, chaplains have played a pivotal role in patient, family member, and staff care. However, little empirical attention has been given to (a) the potential toll of frontline spiritual care on chaplains' mental health and occupational functioning as well as (b) the development of interventions that can help ameliorate these risks and promote resilience. Using a mixed-method practice-based design, we conducted a pilot study ( n = 77) to evaluate a novel spiritually integrated support group intervention for chaplains across multiple industries, which consisted of five Zoom-based sessions cofacilitated by psychotherapists. Participants completed pre- and postintervention measures of traumatic stress, burnout, spiritual/moral struggles, flourishing, resilience, and overall experience in the group. Qualitative findings elucidated the salience of peer support, therapeutic group processes, and key intervention components that warrant further study. Quantitative results indicated significant (a) decreases in burnout and spiritual/moral struggles from pre- to postintervention as well as (b) increases in sense of resilience and flourishing. Findings of this pilot study offer preliminary evidence for the use of a spiritually integrated group model to decrease isolation, address moral and spiritual distress, and promote resilience among chaplains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

At our hospital, universal severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing was performed upon admission and again after 2 inpatient days. As community-wide prevalence, admission, and vaccination rates varied, the number needed to benefit fluctuated between 16 and 769 and the cost per additional detection fluctuated between $800 and $29,400. These 2 metrics were negatively associated with new hospital admissions. No other community indicator was associated with the number needed to benefit and cost per additional detection.

Traumatic injuries to the permanent dentition are most common in children. In severe dentoalveolar injuries, especially avulsion and intrusion, dentoalveolar ankylosis is a common complication, leading to adverse effects on the developing alveolar bone and interfering with the eruption of the adjacent teeth. The decoronation procedure was suggested in 1984 to reduce these side effects related to ankylosis. The objective of the current publication is to describe a minimally invasive, flapless decoronation procedure aimed to minimize and simplify the surgical procedure of decoronation, and ease its clinical acceptance, particularly in young children. The technique is described in a detailed protocol and demonstrated in two cases. Under local anesthesia, the dental crown is removed, and the root is reduced by 1.5-2.0 mm apically to the marginal bone crest. The root canal content is then removed, allowing it to fill with blood. The socket is coronally sealed with a porcine-derived collagen matrix (PDCM) sutured using the "parachute" technique over the resected root, allowing close adaptation to the surrounding soft tissue. In conclusion, the presented technique of flapless decoronation is a modification of the classic decoronation procedure, which can be used as a minimally invasive technique to simplify the surgical procedure and the post-operative process.

Introduction: Using direct peritoneal resuscitation (DPR) as an adjunct when managing patients undergoing damage control laparotomy (DCL) shows promising results. We report our initial experience in utilizing DPR when managing patients who underwent DCL for emergent surgery at the index operation., Materials and Methods: We prospectively collected data on 37 patients between August 2020 to October 2021 who underwent DCL with open abdomens after the index operation and utilized DPR. DPR was performed using peritoneal lavage with DIANEAL PD-2-D 2.5% Ca 3.5 mEq/L at a rate of 400ml/hour. Patients' physiological scores and clinical outcomes were evaluated., Results: 86% required DCL and DPR due to septic abdomen/bowel ischemia. The median (interquartile range [IQR]) age was 62 years (53-70); 62% were male, and median (IQR) body mass index was 30.0kg/m2 (25.5-38.4). On DPR initiation, median (IQR) APACHE-IV score was 48 (33-64) and median (IQR) Acute Physiology Score (APS) was 31 (18-54). After initiation, median (IQR) APACHE-IV score and median (IQR) APS were 39 (21-62) and 19 (11-56), respectively, and both showed significant improvement in survivors (p<0.05). Median (IQR) DPR duration was four days (2-8) and primary abdominal closure was achieved in 30 patients (81%). There were eight mortalities (21.6%) within 30 days postoperatively, of which seven were within 3-24 days due to uncontrolled sepsis/multiple organ failure. The most frequent complication was surgical-site infection recorded in 12 patients (32%). Twenty-four patients (67%) were discharged home/transferred to a rehab center/nursing home., Conclusion: DPR application showed significant improvement of APACHE-IV score and APS in patients with peritonitis/septic abdomen.

Background: Thrombosis (T) is common in coronavirus disease 2019 (COVID-19) patients, and d-dimer concentrations correlate with outcomes. Controversy exists with regards to anticoagulation (AC) for patients. We implemented a full-heparinization AC protocol from the onset of the pandemic and hypothesized that a safety signal would be undetectable. Patients and Methods: Prospective evaluation of 111 patients with COVID-19 critical illness hospitalized from March to June 2020. All patients received therapeutic heparinoid-based AC from admission. Incidences of T, bleeding (B), or both (BT) were noted. The primary outcome was mortality. Kruskal-Wallis test and logistic regression were performed. Results are expressed as n (%), median (interquartile range) and odds ratios with 95% confidence intervals. Alpha was set at 0.05. Results: Thirty-two patients (28%) had T, 23 (20%) had B, and 14 (12%) had BT; 42 (40%) patients were unaffected. Two logistic regression models (outcome = mortality) evaluated BT as T, or BT as B. For BT as T, neither T, B, nor male gender predicted mortality; similarly, for BT as B, neither T, B, nor male gender predicted mortality. Factors associated with higher odds of death included higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; p = 0.0045), higher d-dimer concentration (OR, 1.00; 95% CI, 1.00-1.01; p = 0.043), and higher activated partial thromboplastin time (aPTT; OR, 1.09; 95% CI, 1.02-1.16; p = 0.010). Conclusions: Neither T nor B predicted mortality in this prospective cohort of anticoagulated patients with COVID-19 critical illness. These data support continued full-dose heparinoid prophylaxis.

Background: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression., Methods: We established a medical surveillance team monitoring 63 geriatric institutions in Buenos Aires, Argentina during June-July 2020. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied., Results: After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 54% of pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died. Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027). On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012). No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2)., Conclusions: In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection., Competing Interests: Competing interests: Declaration of interests: I.E., G.B., C.A., M.B., V.Z., C.J.W., M.T.C., D.W., R.L., and G.P.M. declare no conflict of interest. FPP reports grants and non-financial support from Novavax; personal fees from Medimmune, grants and personal fees from Janssen, personal fees from Sanofi, personal fees from Bavarian Nordic, personal fees from Pfizer, personal fees from Merck, personal fees from ArkBio, personal fees from VirBio, personal fees from Regeneron, personal fees from Daiichi Sankyo, all outside the submitted work., (Copyright: © 2022 Esteban I et al.)

Face recognition is a widely accepted biometric identifier, as the face contains a lot of information about the identity of a person. The goal of this study is to match the 3D face of an individual to a set of demographic properties (sex, age, BMI, and genomic background) that are extracted from unidentified genetic material. We introduce a triplet loss metric learner that compresses facial shape into a lower dimensional embedding while preserving information about the property of interest. The metric learner is trained for multiple facial segments to allow a global-to-local part-based analysis of the face. To learn directly from 3D mesh data, spiral convolutions are used along with a novel mesh-sampling scheme, which retains uniformly sampled points at different resolutions. The capacity of the model for establishing identity from facial shape against a list of probe demographics is evaluated by enrolling the embeddings for all properties into a support vector machine classifier or regressor and then combining them using a naive Bayes score fuser. Results obtained by a 10-fold cross-validation for biometric verification and identification show that part-based learning significantly improves the systems performance for both encoding with our geometric metric learner or with principal component analysis.

Objectives: We evaluated rotational thromboelastometry tracings in 44 critically ill coronavirus disease 2019 patients, to determine whether there is a viscoelastic fingerprint and to test the hypothesis that the diagnosis and prediction of venous thromboembolism would be enhanced by the addition of rotational thromboelastometry testing., Results: Rotational thromboelastometry values reflected an increase in clot strength for the EXTEM, INTEM, and FIBTEM assays beyond the reference range. No hyperfibrinolysis was noted. Fibrinolysis shutdown was present but did not correlate with thrombosis; 32% (14/44) of patients experienced a thrombotic episode. For every 1 mm increase of FIBTEM maximum clot formation, the odds of developing thrombosis increased 20% (95% confidence interval, 0-40%, P = .043), whereas for every 1,000 ng/mL increase in D-dimer, the odds of thrombosis increased by 70% (95% confidence interval, 20%-150%, P = .004), after adjustment for age and sex (AUC 0.96, 95% confidence interval, 0.90-1.00). There was a slight but significant improvement in model performance after adding FIBTEM maximum clot formation and EXTEM clot formation time to D-dimer in a multivariable model (P = .04)., Conclusions: D-dimer concentrations were more predictive of thrombosis in our patient population than any other parameter. Rotational thromboelastometry confirmed the hypercoagulable state of coronavirus disease 2019 intensive care unit patients. FIBTEM maximum clot formation and EXTEM clot formation time increased the predictability for thrombosis compared with only using D-dimer. Rotational thromboelastometry analysis is most useful in augmenting the information provided by the D-dimer concentration for venous thromboembolism risk assessment when the D-dimer concentration is between 1,625 and 6,900 ng/dL, but the enhancement is modest. Fibrinolysis shutdown did not correlate with thrombosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fine-grained records of people's interactions, both offline and online, are collected at large scale. These data contain sensitive information about whom we meet, talk to, and when. We demonstrate here how people's interaction behavior is stable over long periods of time and can be used to identify individuals in anonymous datasets. Our attack learns the profile of an individual using geometric deep learning and triplet loss optimization. In a mobile phone metadata dataset of more than 40k people, it correctly identifies 52% of individuals based on their 2-hop interaction graph. We further show that the profiles learned by our method are stable over time and that 24% of people are still identifiable after 20 weeks. Our results suggest that people with well-balanced interaction graphs are more identifiable. Applying our attack to Bluetooth close-proximity networks, we show that even 1-hop interaction graphs are enough to identify people more than 26% of the time. Our results provide strong evidence that disconnected and even re-pseudonymized interaction data can be linked together making them personal data under the European Union's General Data Protection Regulation., (© 2022. The Author(s).)

Objectives: To develop and evaluate a geometric deep-learning network to automatically place seven palatal landmarks on digitized maxillary dental casts., Settings and Sample Population: The sample comprised individuals with permanent dentition of various ethnicities. The network was trained from manual landmark annotations on 732 dental casts and evaluated on 104 dental casts., Materials and Methods: A geometric deep-learning network was developed to hierarchically learn features from point-clouds representing the 3D surface of each cast. These features predict the locations of seven palatal landmarks., Results: Repeat-measurement reliability was <0.3 mm for all landmarks on all casts. Accuracy is promising. The proportion of test subjects with errors less than 2 mm was between 0.93 and 0.68, depending on the landmark. Unusually shaped and large palates generate the highest errors. There was no evidence for a difference in mean palatal shape estimated from manual compared to the automatic landmarking. The automatic landmarking reduces sample variation around the mean and reduces measurements of palatal size., Conclusions: The automatic landmarking method shows excellent repeatability and promising accuracy, which can streamline patient assessment and research studies. However, landmark indications should be subject to visual quality control., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Palatal shape contains a lot of information that is of clinical interest. Moreover, palatal shape analysis can be used to guide or evaluate orthodontic treatments. A statistical shape model (SSM) is a tool that, by means of dimensionality reduction, aims at compactly modeling the variance of complex shapes for efficient analysis. In this report, we evaluate several competing approaches to constructing SSMs for the human palate., Setting and Sample Population: This study used a sample comprising digitized 3D maxillary dental casts from 1,324 individuals., Materials and Methods: Principal component analysis (PCA) and autoencoders (AE) are popular approaches to construct SSMs. PCA is a dimension reduction technique that provides a compact description of shapes by uncorrelated variables. AEs are situated in the field of deep learning and provide a non-linear framework for dimension reduction. This work introduces the singular autoencoder (SAE), a hybrid approach that combines the most important properties of PCA and AEs. We assess the performance of the SAE using standard evaluation tools for SSMs, including accuracy, generalization, and specificity., Results: We found that the SAE obtains equivalent results to PCA and AEs for all evaluation metrics. SAE scores were found to be uncorrelated and provided an optimally compact representation of the shapes., Conclusion: We conclude that the SAE is a promising tool for 3D palatal shape analysis, which effectively combines the power of PCA with the flexibility of deep learning. This opens future AI driven applications of shape analysis in orthodontics and other related clinical disciplines., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: SARS-CoV-2 infected individuals ≥60 years old have the highest hospitalization rates and represent >80% fatalities. Within this population, those in long-term facilities represent >50% of the total COVID-19 related deaths per country. Among those without symptoms, the rate of pre-symptomatic illness is unclear, and potential predictors of progression for symptom development are unknown. Our objective was to delineate the natural evolution of asymptomatic SARS-CoV-2 infection in elders and identify determinants of progression., Methods: We established a medical surveillance team monitoring 63 geriatric institutions. When an index COVID-19 case emerged, we tested all other eligible asymptomatic elders ≥75 or >60 years old with at least 1 comorbidity. SARS-CoV-2 infected elders were followed for 28 days. Disease was diagnosed when any COVID-19 manifestation occurred. SARS-CoV-2 load at enrollment, shedding on day 15, and antibody responses were also studied., Results: After 28 days of follow-up, 74/113(65%) SARS-CoV-2-infected elders remained asymptomatic. 21/39(54%) pre-symptomatic patients developed hypoxemia and ten pre-symptomatic patients died(median day 13.5,IQR 12). Dementia was the only clinical risk factor associated with disease(OR 2.41(95%CI=1.08, 5.39). In a multivariable logistic regression model, dementia remained as a risk factor for COVID-19 severe disease. Furthermore, dementia status showed a statistically significant different trend when assessing the cumulative probability of developing COVID-19 symptoms(log-rank p=0.027). On day 15, SARS-CoV-2 was detectable in 30% of the asymptomatic group while in 61% of the pre-symptomatic(p=0.012). No differences were observed among groups in RT-PCR mean cycle threshold at enrollment(p=0.391) and in the rates of antibody seropositivity(IgM and IgG against SARS-CoV-2 nucleocapsid protein)., Conclusions: In summary, 2/3 of our cohort of SARS-CoV-2 infected elders from vulnerable communities in Argentina remained asymptomatic after 28 days of follow-up with high mortality among those developing symptoms. Dementia and persistent SARS-CoV-2 shedding were associated with progression from asymptomatic to symptomatic infection., Competing Interests: Competing interests: Declaration of interests: I.E., G.B., C.A., M.B., V.Z., C.J.W., M.T.C., D.W., R.L., and G.P.M. declare no conflict of interest. FPP reports grants and non-financial support from Novavax; personal fees from Medimmune, grants and personal fees from Janssen, personal fees from Sanofi, personal fees from Bavarian Nordic, personal fees from Pfizer, personal fees from Merck, personal fees from ArkBio, personal fees from VirBio, personal fees from Regeneron, personal fees from Daiichi Sankyo, all outside the submitted work., (Copyright: © 2021 Esteban I et al.)

The nasal mucosa constitutes the primary entry site for respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the imbalanced innate immune response of end-stage coronavirus disease 2019 (COVID-19) has been extensively studied, the earliest stages of SARS-CoV-2 infection at the mucosal entry site have remained unexplored. Here, we employed SARS-CoV-2 and influenza virus infection in native multi-cell-type human nasal turbinate and lung tissues ex vivo , coupled with genome-wide transcriptional analysis, to investigate viral susceptibility and early patterns of local mucosal innate immune response in the authentic milieu of the human respiratory tract. SARS-CoV-2 productively infected the nasal turbinate tissues, predominantly targeting respiratory epithelial cells, with a rapid increase in tissue-associated viral subgenomic mRNA and secretion of infectious viral progeny. Importantly, SARS-CoV-2 infection triggered robust antiviral and inflammatory innate immune responses in the nasal mucosa. The upregulation of interferon-stimulated genes, cytokines, and chemokines, related to interferon signaling and immune-cell activation pathways, was broader than that triggered by influenza virus infection. Conversely, lung tissues exhibited a restricted innate immune response to SARS-CoV-2, with a conspicuous lack of type I and III interferon upregulation, contrasting with their vigorous innate immune response to influenza virus. Our findings reveal differential tissue-specific innate immune responses in the upper and lower respiratory tracts that are specific to SARS-CoV-2. The studies shed light on the role of the nasal mucosa in active viral transmission and immune defense, implying a window of opportunity for early interventions, whereas the restricted innate immune response in early-SARS-CoV-2-infected lung tissues could underlie the unique uncontrolled late-phase lung damage of advanced COVID-19. IMPORTANCE In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here, we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues infected in parallel with SARS-CoV-2 and influenza virus, we found distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal mucosal infection model can be employed to assess the impact of viral evolutionary changes and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.

Background: Recent efforts in the field of nutritional science have allowed the discovery of disease-beating molecules within foods based on the commonality of bioactive food molecules to FDA-approved drugs. The pioneering work in this field used an unsupervised network propagation algorithm to learn the systemic-wide effect on the human interactome of 1962 FDA-approved drugs and a supervised algorithm to predict anticancer therapeutics using the learned representations. Then, a set of bioactive molecules within foods was fed into the model, which predicted molecules with cancer-beating potential.The employed methodology consisted of disjoint unsupervised feature generation and classification tasks, which can result in sub-optimal learned drug representations with respect to the classification task. Additionally, due to the disjoint nature of the tasks, the employed approach proved cumbersome to optimize, requiring testing of thousands of hyperparameter combinations and significant computational resources.To overcome the technical limitations highlighted above, we represent each drug as a graph (human interactome) with its targets as binary node features on the graph and formulate the problem as a graph classification task. To solve this task, inspired by the success of graph neural networks in graph classification problems, we use an end-to-end graph neural network model operating directly on the graphs, which learns drug representations to optimize model performance in the prediction of anticancer therapeutics., Results: The proposed model outperforms the baseline approach in the anticancer therapeutic prediction task, achieving an F1 score of 67.99%±2.52% and an AUPR of 73.91%±3.49%. It is also shown that the model is able to capture knowledge of biological pathways to predict anticancer molecules based on the molecules' effects on cancer-related pathways., Conclusions: We introduce an end-to-end graph convolutional model to predict cancer-beating molecules within food. The introduced model outperforms the existing baseline approach, and shows interpretability, paving the way to the future of a personalized nutritional science approach allowing the development of nutrition strategies for cancer prevention and/or therapeutics.

Objective: A previous 12-month comparative trial with Criscy™ (r-hGH Cristália), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to Genotropin™. This extension trial evaluated the effects of switching patients treated with Genotropin™ to the biosimilar Criscy™ over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the Criscy™ arm., Design: This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the Genotropin™ arm (n = 39) had the drug replaced by Criscy™ and the remaining participants were kept in the Criscy™ arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events)., Results: Before the switch, both Criscy™ and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ± 1.56 cm/year for Criscy™ group and 8.9 ± 1.36 cm/year for Genotropin™ group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from Genotropin™ to Criscy™ were reported. No neutralizing antibody (nAb) was detected in either group., Conclusions: This trial showed that switching from originator recombinant human growth hormone to Criscy™ had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with Criscy™. Growth rates and ADA incidence remained the same as seen before the switch., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this paper, we introduce a network machine learning method to identify potential bioactive anti-COVID-19 molecules in foods based on their capacity to target the SARS-CoV-2-host gene-gene (protein-protein) interactome. Our analyses were performed using a supercomputing DreamLab App platform, harnessing the idle computational power of thousands of smartphones. Machine learning models were initially calibrated by demonstrating that the proposed method can predict anti-COVID-19 candidates among experimental and clinically approved drugs (5658 in total) targeting COVID-19 interactomics with the balanced classification accuracy of 80-85% in 5-fold cross-validated settings. This identified the most promising drug candidates that can be potentially "repurposed" against COVID-19 including common drugs used to combat cardiovascular and metabolic disorders, such as simvastatin, atorvastatin and metformin. A database of 7694 bioactive food-based molecules was run through the calibrated machine learning algorithm, which identified 52 biologically active molecules, from varied chemical classes, including flavonoids, terpenoids, coumarins and indoles predicted to target SARS-CoV-2-host interactome networks. This in turn was used to construct a "food map" with the theoretical anti-COVID-19 potential of each ingredient estimated based on the diversity and relative levels of candidate compounds with antiviral properties. We expect this in silico predicted food map to play an important role in future clinical studies of precision nutrition interventions against COVID-19 and other viral diseases.

Objectives: To describe the predictive utility of the D-dimer assay among patients with the coronavirus disease 2019 syndrome for unprovoked lower extremity deep venous thrombosis., Design: Prospective observational study with retrospective data analysis., Setting: Academic medical center surgical ICU., Patients: Seventy-two intubated patients with critical illness from coronavirus disease 2019., Interventions: Therapeutic anticoagulation after imaging diagnosis of the first three deep venous thrombosis cases was confirmed; therapeutic anticoagulation as prophylaxis thereafter to all subsequent ICU admissions., Measurements and Main Results: Seventy-two patients with severe coronavirus disease 2019 were screened for deep venous thrombosis after ICU admission with 102 duplex ultrasound examinations, with 12 cases (16.7%) of lower extremity deep venous thrombosis identified. There were no differences between groups with respect to age, renal function, or biomarkers except for D-dimer (median, 12,858 ng/mL [interquartile range, 3,176-30,770 ng/mL] for lower extremity deep venous thrombosis vs 2,087 ng/mL [interquartile range, 638-3,735 ng/mL] for no evidence of deep venous thrombosis; p < 0.0001). Clinical screening tools (Wells score and Dutch Primary Care Rule) had no utility. The C-statistic for D-dimer concentration was 0.874 ± 0.065. At the model-predicted cutoff value of 3,000 ng/mL, sensitivity was 100%, specificity was 51.1%, positive predictive value was 21.8%, and negative predictive value was 100%., Conclusions: Lower extremity deep venous thrombosis is prevalent in coronavirus disease 2019 disease and can be present on ICU admission. Screening has been recommended in the context of the pro-inflammatory, hypercoagulable background milieu. D-dimer concentrations are elevated in nearly all coronavirus disease 2019 patients, and the test appears reliable for screening for lower extremity deep venous thrombosis at or above a concentration of 3,000 ng/mL (more than 13-fold above the normal range). Full anticoagulation is indicated if the diagnosis is confirmed, and therapeutic anticoagulation should be considered for prophylaxis, as all coronavirus disease 2019 patients are at increased risk.

Direct peritoneal resuscitation (DPR) involves instilling 2.5% dextrose peritoneal dialysate into the abdomen in an attempt to both resuscitate the patient and decrease systemic inflammation; 800cc are instilled in the first hour and 400cc/h are instilled each subsequent hour. DPR has been shown to decrease systemic inflammation, increase the rate of primary abdominal closure, lower the rate of intra-abdominal infections, and lower the rate of complications. It also increases blood flow to the intestines, helping to prevent ischemia and re-perfusion injury. We present the technique used for DPR in a patient with an intra-abdominal catastrophe, as well as the use of Kerecis® Omega3 Wound graft (Kerecis, Arlington, VA) and wound vacuum-assisted closure (VAC) for creation of a floating stoma.

Engagement of frontline staff, along with senior leadership, in competition-style healthcare-associated infection reduction efforts, combined with electronic clinical decision support tools, appeared to reduce antibiotic regimen initiations for urinary tract infections (P = .01). Mean monthly standardized infection and device utilization ratios also decreased (P < .003 and P < .0001, respectively).

Purpose: Cushing's disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD., Methods: In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient., Results: Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (- 8.4 mmHg [95% CI - 13.9, - 2.9]) and diastolic blood pressure (- 6.0 mmHg [- 10.0, - 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9-8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score., Conclusions: Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD., Clinical Trial Registration Number: NCT01374906.

Objective: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort., Methods: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases., Conclusions: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

Predicting interactions between proteins and other biomolecules solely based on structure remains a challenge in biology. A high-level representation of protein structure, the molecular surface, displays patterns of chemical and geometric features that fingerprint a protein's modes of interactions with other biomolecules. We hypothesize that proteins participating in similar interactions may share common fingerprints, independent of their evolutionary history. Fingerprints may be difficult to grasp by visual analysis but could be learned from large-scale datasets. We present MaSIF (molecular surface interaction fingerprinting), a conceptual framework based on a geometric deep learning method to capture fingerprints that are important for specific biomolecular interactions. We showcase MaSIF with three prediction challenges: protein pocket-ligand prediction, protein-protein interaction site prediction and ultrafast scanning of protein surfaces for prediction of protein-protein complexes. We anticipate that our conceptual framework will lead to improvements in our understanding of protein function and design.

Objective: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD)., Design: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C., Results: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups., Conclusions: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recent data indicate that up-to 30-40% of cancers can be prevented by dietary and lifestyle measures alone. Herein, we introduce a unique network-based machine learning platform to identify putative food-based cancer-beating molecules. These have been identified through their molecular biological network commonality with clinically approved anti-cancer therapies. A machine-learning algorithm of random walks on graphs (operating within the supercomputing DreamLab platform) was used to simulate drug actions on human interactome networks to obtain genome-wide activity profiles of 1962 approved drugs (199 of which were classified as "anti-cancer" with their primary indications). A supervised approach was employed to predict cancer-beating molecules using these 'learned' interactome activity profiles. The validated model performance predicted anti-cancer therapeutics with classification accuracy of 84-90%. A comprehensive database of 7962 bioactive molecules within foods was fed into the model, which predicted 110 cancer-beating molecules (defined by anti-cancer drug likeness threshold of >70%) with expected capacity comparable to clinically approved anti-cancer drugs from a variety of chemical classes including flavonoids, terpenoids, and polyphenols. This in turn was used to construct a 'food map' with anti-cancer potential of each ingredient defined by the number of cancer-beating molecules found therein. Our analysis underpins the design of next-generation cancer preventative and therapeutic nutrition strategies.

Objective: Employing practice-based research methods, we addressed the need to examine the effectiveness of psychodynamic treatment as a supplement to the efficacy evidence offered by randomized clinical trials., Method: We used person-centered analyses to generate latent subgroups of clients (N = 118; M age  = 40.92; 53.4% female; 81.4% Caucasian; 80.5% heterosexual) receiving contemporary relational psychotherapy (CRP) at a psychodynamic community mental health training clinic., Results: Subgroups of clients reported a change in depression, social conflict, and anxiety symptomatology, and overall life satisfaction, depicted by significant quadratic growth curves. Findings also offered exploratory support for a theoretical proposition from CRP that improved relational functioning would correspond to improved affect dysregulation and overall life satisfaction., Conclusion: Clinical and training implications highlight the need to distinguish subgroups of "responders" and "nonresponders" to inform treatment., (© 2019 Wiley Periodicals, Inc.)

Cyanobacteria inhabiting desert biological soil crusts must prepare towards dehydration, or their revival after rewetting is severely impaired. The mechanisms involved are unknown but signalling of forthcoming dehydration by dawn illumination was demonstrated. Accurate and reproducible simulation of desert conditions enabled examination of physiological activities and transcript profiles in a model organism, Leptolyngbya ohadii, in response to specific conditions. Exposure to far red light or lack of ground warming during dawn severely reduced revival after rewetting and altered the network of gene expression. The data implicated phytochromes in light and temperature sensing. Many genes were up- or down-regulated before water content decline, while others were strongly affected by the progression of dehydration and desiccation. Transcription continues during the desiccated phase but only barely during early rewetting, although photosynthetic activity was regained. Application of rifampicin with or without a preceding dehydration phase demonstrated that RNA is stabilized/protected during desiccation, possibly by intrinsically disordered proteins. We conclude that increasing light and temperature at dawn activates a network of genes that prepare the cells towards dehydration. Quick resumption of photosynthesis upon rewetting in contrast to the slow change in the transcript profile suggested that in addition to preparing towards dehydration the cells also prepare for forthcoming rewetting, during dehydration. Unravelling the presently unknown function of many responding genes will help to clarify the networks involved., (© 2019 John Wiley & Sons Ltd.)

Background: Avian avulavirus-1 (AAvV-1, previously Newcastle Disease Virus) is responsible for poultry and wild birds' disease outbreaks. Numerous whole genome sequencing methods were reported for this virus. These methods included cloning, specific primers amplification, shotgun PCR approaches, Sequence Independent Single Primer Amplification and next generation sequencing platform kits., Methods: Three methods were used to sequence 173 Israeli Avian avulavirus-1 field isolates and one vaccine strain (VH). The sequencing was performed on Proton and Ion Torrent Personal Genome Machine and to a lesser extent, Illumina MiSeq and NextSeq sequencers. Target specific primers (SP) and Sequence Independent Single Primer Amplification (SISPA) products sequenced via the Ion torrent sequencer had a high error rate and truncated genomes. All the next generation sequencing platform sequencing kits generated high sequence accuracy and near-complete genomic size., Results: A high level of mutations was observed in the intergenic regions between the avian avulavirus-1 genes. Within genes, multiple regions are more mutated than the Fusion region currently used for typing., Conclusions: Our findings suggest that the whole genome sequencing by the Ion torrent sequencing kit is sufficient. However, when higher fidelity is desired, the Illumina NextSeq and Proton torrent sequencing kits were found to be preferable., (© 2019 Published by Elsevier B.V.)

Background: Avian avulavirus-1 (AAvV-1, previously Newcastle Disease Virus) is responsible for poultry and wild birds' disease outbreaks. Numerous whole genome sequencing methods were reported for this virus. These methods included cloning, specific primers amplification, shotgun PCR approaches, Sequence Independent Single Primer Amplification and next generation sequencing platform kits., Methods: Three methods were used to sequence 173 Israeli Avian avulavirus-1 field isolates and one vaccine strain (VH). The sequencing was performed on Proton and Ion Torrent Personal Genome Machine and to a lesser extent, Illumina MiSeq and NextSeq sequencers. Target specific primers (SP) and Sequence Independent Single Primer Amplification (SISPA) products sequenced via the Ion torrent sequencer had a high error rate and truncated genomes. All the next generation sequencing platform sequencing kits generated high sequence accuracy and near-complete genomic size., Results: A high level of mutations was observed in the intergenic regions between the avian avulavirus-1 genes. Within genes, multiple regions are more mutated than the Fusion region currently used for typing., Conclusions: Our findings suggest that the whole genome sequencing by the Ion torrent sequencing kit is sufficient. However, when higher fidelity is desired, the Illumina NextSeq and Proton torrent sequencing kits were found to be preferable., (Copyright © 2019. Published by Elsevier B.V.)