Notes

Solution degrees of cytoskeleton remodeling healthy proteins as well as their mRNA expression in tumor tissue of metastatic laryngeal and also hypopharyngeal malignancies.
Restoring a Pro loop residue introduced in the ancestral variant to the corresponding Gly observed in the extant protein led to reduced catalytic activity at high temperatures, with only moderate effects on the melting temperature, supporting the importance of the flexibility of the capping loop in thermoadaptation. Conversely, the inverse Gly to Pro loop mutation in the modern enzyme resulted in a 3-fold increase in the catalytic rate. Despite an overall decrease in maximal activity of ancestor compared to wild type, its increased thermostability provides a robust backbone amenable for further enzyme engineering. Our work cements the importance of loops in enzyme catalysis and provides a molecular mechanism contributing to thermoadaptation in an ancestral enzyme.In this Perspective we present a comprehensive study of the multiple reaction products of metal-free porphyrins (2H-Ps) in contact with the rutile TiO2(110) surface. In the absence of peripheral functionalization with specific linkers, the porphyrin adsorption is driven by the coordination of the two pyrrolic nitrogen atoms of the macrocycle to two consecutive oxygen atoms of the protruding Obr rows via hydrogen bonding. This chemical interaction favours the iminic nitrogen uptake of hydrogen from near surface layers at room temperature, thus yielding a stable acidic porphyrin (4H-P). In addition, a mild annealing (∼100 °C) triggers the incorporation of a Ti atom in the porphyrin macrocycle (self-metalation). We recently demonstrated that such a low temperature reaction is driven by a Lewis base iminic attack, which lowers the energy barriers for the outdiffusion of Ti interstitial atoms (Tiint) [Kremer et al., Appl. Surf. Sci., 2021, 564, 150403]. In the monolayer (ML) range, the porphyrin adsorption site, corresponding to a TiO-TPP configuration, is extremely stable and tetraphenyl-porphyrins (TPPs) may even undergo conformational distortion (flattening) by partial cyclo-dehydrogenation, while remaining anchored to the O rows up to 450 °C [Lovat et al., Nanoscale, 2017, 9, 11694]. Here we show that, upon self-metalation, isolated molecules at low coverage may jump atop the rows of five-fold coordinated Ti atoms (Ti5f). This configuration is associated with the formation of a new coordination complex, Ti-O-Ti5f, as determined by comparison with the deposition of pristine titanyl-porphyrin (TiO-TPP) molecules. The newly established Ti-O-Ti5f anchoring configuration is found to be stable also beyond the TPP flattening reaction. The anchoring of TiO-TPP to the Ti5f rows is, however, susceptible to the cross-talk between phenyls of adjacent molecules, which ultimately drives the TiO-TPP temperature evolution in the ML range along the same pathway followed by 2H-TPP.Sex allocation theory in simultaneous hermaphrodites predicts that optimal sex allocation is influenced by local sperm competition, which occurs when related sperm compete to fertilize a given set of eggs. Different factors, including the mating strategy and the ability to self-fertilize, are predicted to affect local sperm competition and hence the optimal SA. Moreover, since the local sperm competition experienced by an individual can vary temporally and spatially, this can favour the evolution of sex allocation plasticity. Here, using seven species of the free-living flatworm genus Macrostomum, we document interspecific variation in sex allocation, but neither their mating strategy nor their ability to self-fertilize significantly predicted sex allocation among these species. Since we also found interspecific variation in sex allocation plasticity, we further estimated standardized effect sizes for plasticity in response to (i) the presence of mating partners (i.e. in isolation vs. with partners) and (ii) the strength of local sperm competition (i.e. in small vs. large groups). We found that self-fertilization predicted sex allocation plasticity with respect to the presence of mating partners, with plasticity being lower for self-fertilizing species. Finally, we showed that interspecific variation in sex allocation is higher than intraspecific variation due to sex allocation plasticity. Our study suggests that both sex allocation and sex allocation plasticity are evolutionarily labile, with self-fertilization predicting the latter in Macrostomum.The cutaneous side effects of COVID-19 vaccines are being studied and their immunogenicity is most likely linked to the pathophysiology of psoriasis. Although uncommon, several cases of exacerbation and new onset of psoriasis have been reported globally after vaccination. To contribute to the literature on this intriguing topic, we present three cases of de novo psoriasis in adult patients following COVID-19 vaccination. Our observations and a literature review show that this occurrence is independent of the type and brand of vaccines.Anorexia nervosa (AN) is a complex eating disorder that affects multiple organs. 60% of patients have liver injury with transaminitis. The mechanism of liver injury in AN remains unclear. We present a case of a 19-year-old female with AN was admitted to our hospital with marked transaminitis but near normal liver histology on biopsy. Her transaminitis eventually improved as she regained weight. We also conducted a literature review of similar cases to delineate the clinicopathologic spectrum of liver injury in AN patients. Crenolanib mw English published cases of adult AN patients with elevated transaminases who underwent a liver biopsy or autopsy were selected. 32 cases (including ours). All except four patients were female, with median age of 26.5 years and median body mass index 11.9 kg/m2 . Presentations mainly included hypoglycemic coma and weight loss. 63% of patients had severe transaminitis (AST >15x ULN). Other lab findings included elevated international normalized ratio (72%) and hypoalbuminemia (47%). Microscopically, all cases showed intact hepatic architecture. Fibrosis was reported in 12 cases and necroinflamfmation in 8, but only half of each had severe transaminitis. AN patients display a wide spectrum of liver histopathology which often does not correlate with the degree of transaminitis. In severe persistent AN-related transaminitis, liver biopsy is useful to assess the degree of liver injury and to exclude other potential etiologies.Harmful cyanobacterial blooms (cyanoHABs) cause recurrent toxic events in global watersheds. Although public health agencies monitor the causal toxins of most cyanoHABs and scientists in the field continue developing precise detection and prediction tools, the potent anticholinesterase neurotoxin, guanitoxin, is not presently environmentally monitored. This is largely due to its incompatibility with widely employed analytical methods and instability in the environment, despite guanitoxin being among the most lethal cyanotoxins. Here, we describe the guanitoxin biosynthesis gene cluster and its rigorously characterized nine-step metabolic pathway from l-arginine in the cyanobacterium Sphaerospermopsis torques-reginae ITEP-024. Through environmental sequencing data sets, guanitoxin (gnt) biosynthetic genes are repeatedly detected and expressed in municipal freshwater bodies that have undergone past toxic events. Knowledge of the genetic basis of guanitoxin biosynthesis now allows for environmental, biosynthetic gene monitoring to establish the global scope of this neurotoxic organophosphate.
Infected wounds extend healing time and are associated with higher treatment costs than noninfected wounds. Several observational studies indicate that negative-pressure wound therapy with instillation can effectively reduce bacterial bioburden and improve wound healing. Only a few randomized trials with small sample sizes have been published, and a meta-analysis directly comparing negative-pressure wound therapy with instillation to current standard care is lacking. It is therefore uncertain whether negative-pressure wound therapy with instillation actually improves wound healing. The authors performed a systematic review and hypothesized that negative-pressure wound therapy with instillation reduces wound closure time.

The PubMed, Embase, and CENTRAL databases were searched up to December of 2020 for English studies that compare negative-pressure wound therapy with instillation-to either negative-pressure wound therapy without instillation or to other types of wound care-for the treatment of acute or chufficient evidence to support or discard the use of negative-pressure wound therapy with instillation for infected wounds. More randomized trials are needed to determine whether a beneficial effect can be substantiated.
To assess the association between internal medicine (IM) residents' race/ethnicity and clinical performance assessments.

The authors conducted a cross-sectional analysis of clinical performance assessment scores at 6 U.S. IM residency programs from 2016 to 2017. Residents underrepresented in medicine (URiM) were identified using self-reported race/ethnicity. Standardized scores were calculated for Accreditation Council for Graduate Medical Education core competencies. Cross-classified mixed-effects regression assessed the association between race/ethnicity and competency scores, adjusting for rotation time of year and setting; resident gender, postgraduate year, and IM In-Training Examination percentile rank; and faculty gender, rank, and specialty.

Data included 3,600 evaluations by 605 faculty of 703 residents, including 94 (13.4%) URiM residents. Resident race/ethnicity was associated with competency scores, with lower scores for URiM residents (difference in adjusted standardized scores between URiMs of a noninclusive learning environment, or structural inequities in assessment.
Resident race/ethnicity was associated with assessment scores to the disadvantage of URiM residents. This may reflect bias in faculty assessment, effects of a noninclusive learning environment, or structural inequities in assessment.Defects involving the midface and maxilla pose unique challenges to reconstructive surgeons. The maxilla serves as the central keystone of the face and interfaces with various other facial subunits to affect form and function. Reconstructive methods range from prosthetics to free tissue transfer, and the indications for different options are reviewed here. Finally, special considerations including management of the orbit, dental rehabilitation, and future directions are discussed.We report a water-soluble AIEgen (TYDL) to be self-assembled into fluorescent organic nanoparticles (TYDLs) for specific sensing of SO2 in living hepatoma cells. It is demonstrated that the TYDLs were suitable for ratiometrically detecting endogenous and exogenous SO2 in mitochondria with good selectivity, low detection limit (75 nM) and excellent photostability (>30 min). These findings imply the great potential applications of TYDLs for the diagnosis of SO2-related diseases in cell biology.In the wake of the Black Lives Matter and other antiracism justice movements, medical education is evolving to incorporate health equity principles for all medical students and residents, while also increasing institutional diversity recruitment of minoritized physicians. As the demographics of U.S. medical trainees shift to reflect a rapidly evolving patient population, the prevalence of culturally concordant patient-physician visits, where patients share elements of language, religion, customs, and identities with their physician, is also expected to increase. However, existing antiracist curricula are standardized to all learners and there is a dearth of cultural sensitivity training designed specifically for minoritized learners to interrogate the culturally concordant space they share with patients and mentors. In this article, the authors propose a new model for minoritized learners' cultural training, culturally reflective medicine (CRM) that identifies unanticipated tensions that may arise as minoritized learners bridge both White and Eurocentric professional and personal identities, examines how intersectionality can both strengthen encounters and lead to shared blind spots, and empowers minoritized physicians with tools for self- and group reflection to advocate for their communities.
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