Establishing reaction networks in the 16-electron sulfur reduction reaction.

The sulfur reduction reaction (SRR) plays a central role in high-capacity lithium sulfur (Li-S) batteries. The SRR involves an intricate, 16-electron conversion process featuring multiple lithium polysulfide intermediates and reaction branches1-3. Establishing the complex reaction network is essential for rational tailoring of the SRR for improved Li-S batteries, but represents a daunting challenge4-6. Herein we systematically investigate the electrocatalytic SRR to decipher its network using the nitrogen, sulfur, dual-doped holey graphene framework as a model electrode to understand the role of electrocatalysts in acceleration of conversion kinetics. Combining cyclic voltammetry, in situ Raman spectroscopy and density functional theory calculations, we identify and directly profile the key intermediates (S8, Li2S8, Li2S6, Li2S4 and Li2S) at varying potentials and elucidate their conversion pathways. Li2S4 and Li2S6 were predominantly observed, in which Li2S4 represents the key electrochemical intermediate dictating the overall SRR kinetics. Li2S6, generated (consumed) through a comproportionation (disproportionation) reaction, does not directly participate in electrochemical reactions but significantly contributes to the polysulfide shuttling process. We found that the nitrogen, sulfur dual-doped holey graphene framework catalyst could help accelerate polysulfide conversion kinetics, leading to faster depletion of soluble lithium polysulfides at higher potential and hence mitigating the polysulfide shuttling effect and boosting output potential. These results highlight the electrocatalytic approach as a promising strategy for tackling the fundamental challenges regarding Li-S batteries.

Chiral molecular intercalation superlattices.

The discovery of chiral-induced spin selectivity (CISS) opens up the possibility to manipulate spin orientation without external magnetic fields and enables new spintronic device designs1-4. Although many approaches have been explored for introducing CISS into solid-state materials and devices, the resulting systems so far are often plagued by high inhomogeneity, low spin selectivity or limited stability, and have difficulties in forming robust spintronic devices5-8. Here we report a new class of chiral molecular intercalation superlattices (CMIS) as a robust solid-state chiral material platform for exploring CISS. The CMIS were prepared by intercalating layered two-dimensional atomic crystals (2DACs) (such as TaS2 and TiS2) with selected chiral molecules (such as R-α-methylbenzylamine and S-α-methylbenzylamine). The X-ray diffraction and transmission electron microscopy studies demonstrate highly ordered superlattice structures with alternating crystalline atomic layers and self-assembled chiral molecular layers. Circular dichroism studies show clear chirality-dependent signals between right-handed (R-) and left-handed (S-) CMIS. Furthermore, by using the resulting CMIS as the spin-filtering layer, we create spin-selective tunnelling junctions with a distinct chirality-dependent tunnelling current, achieving a tunnelling magnetoresistance ratio of more than 300 per cent and a spin polarization ratio of more than 60 per cent. With a large family of 2DACs of widely tunable electronic properties and a vast selection of chiral molecules of designable structural motifs, the CMIS define a rich family of artificial chiral materials for investigating the CISS effect and capturing its potential for new spintronic devices.

Approaching the intrinsic exciton physics limit in two-dimensional semiconductor diodes.

Two-dimensional (2D) semiconductors have attracted intense interest for their unique photophysical properties, including large exciton binding energies and strong gate tunability, which arise from their reduced dimensionality1-5. Despite considerable efforts, a disconnect persists between the fundamental photophysics in pristine 2D semiconductors and the practical device performances, which are often plagued by many extrinsic factors, including chemical disorder at the semiconductor-contact interface. Here, by using van der Waals contacts with minimal interfacial disorder, we suppress contact-induced Shockley-Read-Hall recombination and realize nearly intrinsic photophysics-dictated device performance in 2D semiconductor diodes. Using an electrostatic field in a split-gate geometry to independently modulate electron and hole doping in tungsten diselenide diodes, we discover an unusual peak in the short-circuit photocurrent at low charge densities. Time-resolved photoluminescence reveals a substantial decrease of the exciton lifetime from around 800 picoseconds in the charge-neutral regime to around 50 picoseconds at high doping densities owing to increased exciton-charge Auger recombination. Taken together, we show that an exciton-diffusion-limited model well explains the charge-density-dependent short-circuit photocurrent, a result further confirmed by scanning photocurrent microscopy. We thus demonstrate the fundamental role of exciton diffusion and two-body exciton-charge Auger recombination in 2D devices and highlight that the intrinsic photophysics of 2D semiconductors can be used to create more efficient optoelectronic devices.

Nuclear miR-204-3p mitigates metabolic dysfunction-associated steatotic liver disease in mice.

BACKGROUND & AIMS: Accumulating evidence has indicated the presence of mature microRNAs (miR) in the nucleus, but their effects on steatohepatitis remain elusive. We have previously demonstrated that the intranuclear miR-204-3p in macrophages protects against atherosclerosis, which shares multiple risk factors with metabolic dysfunction-associated steatotic liver disease (MASLD). Herein, we aimed to explore the functional significance of miR-204-3p in steatohepatitis. METHODS: miR-204-3p levels and subcellular localization were assessed in the livers and peripheral blood mononuclear cells of patients with MASLD. Wild-type mice fed high-fat or methionine- and choline-deficient diets were injected with an adeno-associated virus system containing miR-204-3p to determine the effect of miR-204-3p on steatohepatitis. Co-culture systems were applied to investigate the crosstalk between macrophages and hepatocytes or hepatic stellate cells (HSCs). Multiple high-throughput epigenomic sequencings were performed to explore miR-204-3p targets. RESULTS: miR-204-3p expression decreased in livers and macrophages in mice and patients with fatty liver. In patients with MASLD, miR-204-3p levels in peripheral blood mononuclear cells were inversely related to the severity of hepatic inflammation and damage. Macrophage-specific miR-204-3p overexpression reduced steatohepatitis in high-fat or methionine- and choline-deficient diet-fed mice. miR-204-3p-overexpressing macrophages inhibited TLR4/JNK signaling and pro-inflammatory cytokine release, thereby limiting fat deposition and inflammation in hepatocytes and fibrogenic activation in HSCs. Epigenomic profiling identified miR-204-3p as a specific regulator of ULK1 expression. ULK1 transcription and VPS34 complex activation by intranuclear miR-204-3p improved autophagic flux, promoting the anti-inflammatory effects of miR-204-3p in macrophages. CONCLUSIONS: miR-204-3p inhibits macrophage inflammation, coordinating macrophage actions on hepatocytes and HSCs to ameliorate steatohepatitis. Macrophage miR-204-3p may be a therapeutic target for MASLD. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic inflammatory disease ranging from simple steatosis to steatohepatitis. However, the molecular mechanisms underlying the progression of MASLD remain incompletely understood. Here, we demonstrate that miR-204-3p levels in circulating peripheral blood mononuclear cells are negatively correlated with disease severity in patients with MASLD. Nuclear miR-204-3p activates ULK1 transcription and improves autophagic flux, limiting macrophage activation and hepatic steatosis. Our study provides a novel understanding of the mechanism of macrophage autophagy and inflammation in steatohepatitis and suggests that miR-204-3p may act as a potential therapeutic target for MASLD.

The effect of somatic pain and comorbid mental distress on oral health-related quality of life in orthodontic patients.

OBJECTIVES: The purpose of the present study was to evaluate the prevalence of somatic pain in orthodontic patients and determine whether somatic pain contributes to worsening oral health-related quality of life (OHRQoL) through the mediating effect of psychological discomfort. MATERIALS AND METHODS: Scale measurements and analyses were conducted on a cohort of 769 orthodontic outpatients, encompassing Patient Health Questionnaire-15-pain (PHQ-15-P), Hua-Xi Emotional-Distress Index (HEI), Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ), and Oral Health Impact Profile-14 (OHIP-14). RESULTS: Among the respondents, 56.3% (N = 433) reported somatic pain and 20.0% (N = 154) had mental discomfort based on PHQ-15-P and HEI scores. Patients with somatic pain symptoms had significantly higher scores of HEI and OHIP-14 (P < 0.001), and higher PHQ-15-P and HEI scores emerged as statistically significant predictors of lower OHIP-14 scores (P < 0.001). HEI scores which assessed anxiety and depression partially mediated the correlation between PHQ-15-P and OHIP-14 scores, of which anxiety accounted for 52.9% of the overall mediation effect, dominating the indirect effect. CONCLUSION: Orthodontic patients reporting somatic pains were at a significantly higher risk of worsening OHRQoL during treatment, and this adverse effect is partially mediated by anxiety and depression. CLINICAL RELEVANCE: Our findings highlight the necessity for the assessment of general health and mental well-being during orthodontic interventions. To prevent delays in treating general disorders and the potential failure of orthodontic treatments, we encourage increased attentiveness towards patients with somatic symptoms and consideration of the adverse effects of comorbid mental distress.

Identification of genes associated with fatty acid biosynthesis based on 214 safflower core germplasm.

BACKGROUND: Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood. RESULTS: In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H0), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil. CONCLUSIONS: Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.

Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.

OBJECTIVES: Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence. MATERIALS AND METHODS: Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading in vitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6 -methyladenosine (m6 A) modification were evaluated. The role of m6 A modification in chondrocyte senescence was determined. The therapeutic effects of m6 A inhibition in TMJOA were investigated. RESULTS: Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence in vitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6 A modification. Moreover, inhibition of m6 A modification rescued chondrocyte senescence in vitro and in vivo, and suppressed TMJOA progression in rats. CONCLUSIONS: This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6 A inhibition in TMJOA.

Effect of offset on the precision of 3D-printed orthognathic surgical splints.

OBJECTIVE: This study evaluated the effect of offset on the precision of three-dimensional (3D)-printed splints, proposing to optimize the splint design to compensate for systematic errors. MATERIALS AND METHODS: 14 resin model sets were scanned and offset as a whole by given distances (0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, and 0.40 mm). Intermediate splints (ISs) and final splints (FSs) were generated from the non-offset and offset models and grouped correspondingly, named as splint type-offset value, IS-0.05, for instance. Dentitions occluded with the splint were scanned. Translational and rotational deviations of the lower dentition relative to the upper dentition were 3D measured. RESULTS: Deviations of ISs and FSs were more evident in the vertical and pitch dimensions, and were mostly acceptable in other dimensions. ISs with offset ≥ 0.05 mm showed vertical deviations significantly below 1 mm (P < 0.05) while ISs with 0.10- to 0.30-mm offsets had pitch rotations significantly lower than 1° (P < 0.05). The Pitch of IS-0.35 was significantly larger than ISs with 0.15- to 0.30-mm offsets (P < 0.05). Meanwhile, FSs fit better as the offset increased and FSs with offsets ≥ 0.15 mm all had deviations significantly lower than 1 mm (for translation) or 1° (for rotation) (P < 0.05). CONCLUSIONS: Offset affects the precision of 3D-printed splints. Moderate offset values of 0.10 to 0.30 mm are recommendable for ISs. Offset values ≥ 0.15 mm are recommended for FSs in cases with stable final occlusion. CLINICAL RELEVANCE: This study found the optimal offset ranges for 3D-printed ISs and FSs via a standardized protocol.

Construction of 131I-RGDyC-PEG-PAMAM-DTX targeted drug delivery system and study of its physicochemical properties and biological activity.

OBJECTIVE: To construct a novel targeted drug delivery nanoprobe: iodine-131-arginine-glycine-aspartate-tyrosine-cysteine peptide-polyethylene glycol-fifth generation polyamide-amine-docetaxel (131I-RGDyC-PEG-PAMAM-DTX) and to investigate its physicochemical properties and biological activity. MATERIALS AND METHODS: Docetaxel was wrapped by solvent volatilization method, and the regression curve of DTX was constructed by high-performance liquid chromatography to determine its drug loading. The particle size of RGDyC-PEG-PAMAM-DTX was detected by dynamic light scattering. The 131I labeling was performed by a chloramine-T method and purified by Sephadex-G50 column chromatography, and it is in vitro stability and lipid-water partition coefficient was investigated. The cytotoxicity of RGDyC-PEG-PAMAM-DTX and 131I-RGDyC-PEG-PAMAM-DTX on A549 cells in vitro was detected by Cell Counting Kit-8 assay. RESULTS: Arginine-glycine-aspartate-tyrosine-cysteine peptide-PEG-PAMAM-DTX was successfully prepared by solvent volatilization with a loading capacity of about 44µg/mg. The average particle size of RGDyC-PEG-PAMAM-DTX was 57.8nm; the labeling rate of 131I-RGDyC-PEG-PAMAM-DTX by the chloramine-T method was 74.09%-76.09%, and the radiochemical purity was 88.9%-92.6% after purification. The in vitro stability showed that the radiochemical purity was above 80% after 72h in fetal bovine serum and PBS buffer (25oC and 37oC).CCK-8 assay showed that RGDyC-PEG-PAMAM-DTX and 131I-RGDyC-PEG-PAMAM-DTX had more pronounced cytotoxic effects than free DTX and 131I. CONCLUSION: Iodine-131-RGDyC-PEG-PAMAM-DTX has good physicochemical properties and apparent cytotoxic effectsandis expected to be used in treating tumors.

Endophthalmitis Rates among Medicare Beneficiaries Undergoing Cataract Surgery between 2011 and 2019.

PURPOSE: To determine national incidence and risk factors associated with developing endophthalmitis after cataract surgery in the United States. DESIGN: Retrospective, cross-sectional analysis. PARTICIPANTS: Medicare beneficiaries aged ≥65 years undergoing cataract surgery between 2011 and 2019. METHODS: Medicare claims were used to identify all patients who underwent ≥1 cataract surgery between 2011 and 2019. Endophthalmitis cases within 90 days of the cataract surgery were identified using diagnostic codes. Patients with a history of endophthalmitis 12 months before their cataract surgery procedure were excluded. Annual and aggregate 9-year incidences were determined for all cataract surgeries and for stand-alone cataract procedures. A stepwise multivariable logistic regression model using generalized estimating equations was used to evaluate factors associated with occurrence of postoperative endophthalmitis. MAIN OUTCOME MEASURES: The 90-day postoperative endophthalmitis rate and patient risk factors associated with onset of endophthalmitis after cataract surgery. RESULTS: A total of 14 396 438 cataract surgeries were performed among Medicare beneficiaries between 2011 and 2019. The overall 90-day postoperative endophthalmitis rate was 1.36 per 1000 cataract surgeries for all cataract procedures and 1.30 per 1000 cataract surgeries for stand-alone cataract procedures. A decreasing trend was noted for postoperative endophthalmitis rates during the 9-year study period. On multivariable analysis, the risk of endophthalmitis after cataract surgery was increased for cases performed among those aged ≥75 years versus those aged <75 years (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.11-1.18), Blacks (OR, 1.13; 95% CI, 1.07-1.20), Native Americans (OR, 1.43; 95% CI, 1.19-1.73), and eyes with any history of invasive glaucoma surgery (OR, 1.40; 95% CI, 1.18-1.65). Cataract cases combined with retinal surgery (OR, 2.60; 95% CI, 2.15-3.16) and those performed when the Charlson Comorbidity Index (CCI) was greater than 0 also had an increased likelihood of developing endophthalmitis. The risk of endophthalmitis was lower for cases performed on women versus men (OR, 0.89; 95% CI, 0.86-0.92). CONCLUSIONS: The overall 90-day postoperative endophthalmitis rate after cataract surgery was 1.36 per 1000 cataract surgeries between 2011 and 2019. Patient age, gender, race, and CCI were associated with risk of endophthalmitis.

Comparison of propofol-nalbuphine and propofol-fentanyl sedation for patients undergoing endoscopic retrograde cholangiopancreatography: a double-blind, randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been increasingly used to treat patients with biliary/pancreatic duct obstruction or stricture outside the operating room. Effective and safe sedation techniques are needed because of painful stimuli and the long duration of the ERCP procedure.Nalbuphine has been shown to cause less respiratory depression during sedation than similar cases without nalbuphine. This study compared the effects of propofol-nalbuphine (PN) and propofol-fentanyl (PF) sedation in patients undergoing ERCP. METHODS: Four hundred patients scheduled for ERCP procedures were divided into two groups: the PF group (receiving PF sedation,n = 199) and the PN group (receiving PN sedation,n = 201). Vital signs, adverse events during surgery, patient movement scores, pain scores, and adverse events one day post-ERCP were recorded. RESULTS: Stable haemodynamics were observed in both groups.Compared to the PF group, the PN group showed significantly decreased respiratory depression (P < 0.0001) and surgical interruptions (P = 0.048).Nalbuphine decreased patient movement by reducing pain from ERCP. CONCLUSION: Nalbuphine, instead of fentanyl, precipitated less respiratory depression while permitting adequate/equivalent sedation for ERCP and therefore provides more efficient and safer sedation. Trial registration ChiCTR, ChiCTR1800016018, Registered 7 May 2018, http://www.chictr.org.cn/showproj.aspx?proj=27085.

Orthodontic correction of a skeletal Class II malocclusion with severe gummy smile by total intrusion of the maxillary dentition.

A 22-year-old woman visited the hospital complaining of lip protrusion, crowded teeth, and a gummy smile. The clinical examination showed a convex profile with a hyperdivergent mandible and a severe gummy smile in both anterior and posterior regions. The unstable mandible position was considered during treatment planning, and a targeted mechanic system was carefully designed. Temporary skeletal anchorage devices in the posterior dental region and a transpalatal arch were introduced as anchorage for the intrusion of the entire maxillary dentition and controlled retraction of the anterior teeth. Based on effective and simple mechanisms, we successfully eliminated the severe gummy smile and improved the facial aesthetics with the aid of conventional appliances. This approach provided an alternative option to orthognathic surgery or bulky invasive miniscrews for treatment of skeletal Class II malocclusion with severe gummy smile.

Integrating maxillary dentition and 3D facial photo using a modified CAD/CAM facebow.

BACKGROUND: Accurate integration of the dentitions with the face is essential in dental clinical practice. Here we introduce a noninvasive and efficient protocol to integrate the digitized maxillary dentition with the three-dimensional (3D) facial photo using a prefabricated modified computer-aided design/computer-aided manufacture (CAD/CAM) facebow. METHODS: To integrate the maxillary dentition with the 3D facial photo, the CAD/CAM facebow protocol was applied to 20 patients by taking a series of 3D facial photos in the clinic and integrating them in the laboratory. The integration accuracy of this protocol was compared with that of a valid 3D computed tomography (CT)-aided protocol concerning translational deviations of the landmarks representing maxillary incisors and maxillary first molars as well as the rotational deviation of the maxillary dentition. The intra- and inter-observer reproducibility was assessed, and the time of clinical operation and laboratory integration was recorded. RESULTS: This facebow-aided protocol generated 3D fused images with colored faces and high-resolution dentitions, and showed high reproducibility. Compared with the well-established CT-aided protocol, the translational deviations ranged from 0 to 1.196 mm, with mean values ranging from 0.134 to 0.444 mm, and a relatively high integration error was found in the vertical dimension (Z) with a mean ± standard deviation (SD) of 0.379 ± 0.282 mm. Meanwhile, the rotational deviations ranged from 0.020 to 0.930°, with mean values less than 1°, and the most evident deviation was seen in pitch rotation with a mean ± SD of 0.445 ± 0.262°. The workflow took 4.34 ± 0.19 min (mins) for clinical operation and 11.23 ± 0.29 min for laboratory integration. CONCLUSION: The present radiation-free protocol with the modified CAD/CAM facebow provided accurate and reproducible transfer of the digitized maxillary dentition to the 3D facial photo with high efficiency.

Effect of occlusal coverage depths on the precision of 3D-printed orthognathic surgical splints.

BACKGROUND: Precise orthognathic surgical splints are important in surgical-orthodontic treatment. This study aimed to propose a standardized protocol for three-dimensional (3D)-printed splints and assess the precision of splints with different occlusal coverage on the dentition (occlusal coverage depth, OCD), thus optimizing the design of 3D-printed splints to minimize the seemingly unavoidable systematic errors. METHODS: Resin models in optimal occlusion from 19 patients were selected and scanned. Intermediate splints (ISs) and final splints (FSs) with 2-mm, 3-mm, 4-mm, and 5-mm OCDs were fabricated and grouped as IS-2, IS-3, IS-4, IS-5, FS-2, FS-3, FS-4, and FS-5, respectively. The dentitions were occluded with each splint and scanned as a whole to compare with the original occlusion. Translational and rotational deviations of the lower dentition and translational deviations of the landmarks were measured. RESULTS: For vertical translation, the lower dentitions translated inferiorly to the upper dentition in most of the splints, and the translation increased as OCD got larger. Vertical translations of the dentitions in 89.47% of IS-2, 68.42% of IS-3, 42.11% of IS-4, 10.53% of IS-5, 94.74% of FS-2, 63.16% of FS-3, 26.32% of FS-4, and 21.05% of FS-5 splints were below 1 mm, respectively. For pitch rotation, the lower dentitions rotated inferiorly and posteriorly in most groups, and the rotation increased as OCD got larger. Pitch rotations of the dentitions in 100% of IS-2, 89.47% of IS-3, 57.89% of IS-4, 52.63% of IS-5, 100.00% of FS-2, 78.95% of FS-3, 52.63% of FS-4, and 47.37% of FS-5 splints were below 2°, respectively. On the other hand, the transversal and sagittal translations, roll and yaw rotations of most groups were clinically acceptable (translation < 1 mm and rotation < 2°). The deviations of ISs and FSs showed no statistical significance at all levels of coverage (P > 0.05). CONCLUSIONS: A protocol was proposed to generate 3D-printed ISs and FSs with normalized basal planes and standardized OCDs. Deviations of the ISs and FSs were more evident in the vertical dimension and pitch rotation and had a tendency to increase as the OCD got larger. ISs and FSs with both 2-mm and 3-mm OCD are recommendable regarding the precision relative to clinical acceptability. However, considering the fabrication, structural stability, and clinical application, ISs and FSs with 3-mm OCD are recommended for accurate fitting.

The vital role of Gli1+ mesenchymal stem cells in tissue development and homeostasis.

The hedgehog (Hh) signaling pathway plays an essential role in both tissue development and homeostasis. Glioma-associated oncogene homolog 1 (Gli1) is one of the vital transcriptional factors as well as the direct target gene in the Hh signaling pathway. The cells expressing the Gli1 gene (Gli1+ cells) have been identified as mesenchymal stem cells (MSCs) that are responsible for various tissue developments, homeostasis, and injury repair. This review outlines some recent discoveries on the crucial roles of Gli1+ MSCs in the development and homeostasis of varieties of hard and soft tissues.

Underutilization of Needle Biopsy Before Breast Surgery: A Measure of Low-Value Care.

BACKGROUND: Breast core needle biopsy (CNB) can obviate the need for breast surgery in patients with an unknown breast lesion; however, variation in compliance with this guideline may represent a disparity in health care and a surrogate measure of unnecessary surgery. We evaluated variation in breast CNB rates prior to initial breast cancer surgery. METHODS: We performed a retrospective analysis using Medicare claims from 2015 to 2017 to evaluate the proportion of patients who received a CNB within 6 months prior to initial breast cancer surgery. Outlier practice pattern was defined as a preoperative CNB rate ≤ 70%. Logistic regression was used to evaluate surgeon characteristics associated with outlier practice pattern. RESULTS: We identified 108,935 female patients who underwent initial breast cancer surgery performed by 3229 surgeons from July 2015 to June 2017. The mean CNB rate was 86.7%. A total of 7.7% of surgeons had a CNB performed prior to initial breast surgery ≤ 70% of the time, and 2.0% had a CNB performed ≤ 50% of the time. Outlier breast surgeons were associated with practicing in a micropolitan area (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.29-2.73), in the South (OR 1.84, 95% CI 1.20-2.84) or West region (OR 1.78, 95% CI 1.11-2.86), > 20 years in practice (OR 1.52, 95% CI 1.09-2.11), and low breast cancer surgery volume (< 30 cases in the study period; OR 4.03, 95% CI 2.75-5.90). CONCLUSIONS: Marked variation exists in whether a breast core biopsy is performed prior to initial breast surgery, which may represent unnecessary surgery on individual patients. Providing surgeon-specific feedback on guideline compliance may reduce unwarranted variation.

Contemporary Trends in Physician Utilization Rates of CEA and CAS for Asymptomatic Carotid Stenosis among Medicare Beneficiaries.

BACKGROUND: Carotid revascularization for asymptomatic carotid artery stenosis (ACAS) has become increasingly controversial in the past few decades as the best medical therapy has improved. The aim of this study was to assess and define contemporary trends in the rate of carotid revascularization procedures for ACAS in the United States and to characterize outlier physicians performing a higher rate of asymptomatic revascularization compared to their peers. METHODS: We used 100% Medicare fee-for-service claims to identify all patients who were newly diagnosed with ACAS between 01/2011-06/2018. Patients with symptomatic carotid artery stenosis, those with prior carotid revascularization, and surgeons who performed ≤10 CEAs during the study period were excluded. We used a hierarchical multivariable logistic regression model to evaluate patient and physician characteristics associated with undergoing a carotid endarterectomy or carotid artery stent procedure within 3 months after the initial diagnosis of ACAS. We also assessed temporal trends in carotid revascularization rates over time using the Cochran-Armitage Trend Test. RESULTS: Overall, 795,512 patients (median age 73.9 years, 50.9% male, 87.6% white) had a first-time diagnosis of ACAS during the study period, of which 23,481 (3.0%) underwent carotid revascularization within 3 months. There was a significant decline in overall carotid artery revascularization rates over time (2011: 3.2% vs. 2018: 2.1%; P < 0.001). The median and mean physician-specific carotid revascularization rates were 2.0% (IQR 0.0%-6.3%) and 4.7% ± 7.1%, respectively. Three-hundred and fifty physicians (5.2%) had carotid revascularization rates ≥19%, which was more than 2 standard deviations above the mean. After adjusting for patient-level characteristics, physician-level variables associated with carotid revascularization for newly diagnosed ACAS included male sex (adjusted OR 1.59, 95% CI 1.35-1.89), more years in practice (≥31 vs. <10 years, aOR 1.64, 95% CI 1.32-2.04), rural practice location (aOR 1.34, 95% CI 1.18-1.52), Southern region practice location (versus Northeast, aOR 1.54, 95% CI 1.39-1.69), and lower volume of ACAS patients (lower versus upper tertile, aOR 2.62, 95% CI 2.39-2.89). Cardiothoracic surgeons had a 1.52-fold higher odds of carotid revascularization compared to vascular surgeons (95% CI 1.36-1.68), whereas cardiologists and radiologists had lower intervention rates (both, P < 0.05). CONCLUSIONS: The current early revascularization rate for newly diagnosed ACAS is <5% among proceduralists in the United States, and has been decreasing steadily since 2014. There are particular physician-level characteristics that are associated with higher rates of carotid revascularization that cannot be fully contextualized without high-level contemporary outcomes data to guide decision making in ACAS.

van der Waals Integrated Devices Based on Nanomembranes of 3D Materials.

van der Waals (vdW) integration offers a flexible strategy to nearly arbitrarily combine materials of radically different chemical compositions, crystal structures, or lattice orientations, enabling versatile heterostructures with unique electronic and photonic characteristics or other exotic properties that are difficult to access in traditional epitaxial heterostructures, as highlighted by a recent blossom in two-dimensional (2D) vdW heterostructures. However, the studies on vdW heterostructures currently have been largely limited to 2D materials, with few reports of vdW integration of traditional three-dimensional (3D) materials. Here, we show that the vdW integration approach could be extended to 3D materials for flexible integration of highly disparate materials. In particular, by assembling nanomembranes fabricated from bulk ß-gallium oxide, silicon, and platinum, we demosntrate a variety of functional devices including Schottky diodes, p-n diodes, metal-semiconductor field-effect transistors, and junction field-effect transistors. These devices exhibit excellent electronic performance, in terms of ideality factor, current on/off ratio, and subthreshold swing, laying the foundations for constructing high-performance heterostructure devices.

Diagnostic and treatment protocol for a patient with temporomandibular disorder using a stabilization splint and temporary anchorage devices.

Treatment of orthodontic patients with temporomandibular disorder (TMD) is challenging for orthodontists because of the TMD signs and symptoms and unstable mandible position, which may lead to improper diagnosis and treatment design. This case report presents a 22-year-old woman with proclined maxillary incisors and TMD. First, stabilization splint therapy was implemented to eliminate temporomandibular joint pain and to obtain the stable adapted centric posture. Subsequently, orthodontic treatment was initiated on the basis of a definitive diagnosis made from the postsplint records. Temporary anchorage devices were used to intrude maxillary molars and distalize the maxillary dental arch. Favorable soft tissue, skeletal, and dental relationship were accomplished after 12 months of comprehensive orthodontic treatment. Functional occlusion was established with teeth as well as vacuum-formed retainers. Excellent posttreatment stability was maintained after a 20-month retention.

Prescribing Patterns and Costs Associated with Postoperative Eye Drop Use in Medicare Beneficiaries Undergoing Cataract Surgery.

PURPOSE: To determine costs and prescribing patterns of postoperative eye drops for cataract surgery and estimate potential savings of generic or therapeutic drug substitutions. DESIGN: Retrospective, cross-sectional analysis. PARTICIPANTS: Medicare beneficiaries aged ≥65 years with Part D coverage who underwent cataract surgery in 2016. METHODS: Medicare Part D claims were used to extract information on eye drop prescriptions that were filled during the postoperative period of cataract surgery. Savings from generic or therapeutic drug substitutions were estimated for brand medications. MAIN OUTCOME MEASURES: Total cost of postoperative eye drops for cataract surgery and physician and patient factors associated with medication cost. RESULTS: Postoperative eye drops were prescribed in 2016 to 88% of 591 733 Medicare beneficiaries who underwent cataract surgery during that calendar year, with brand medications accounting for 57.5% of prescription volume. The overall cost totaled more than $167 million, 76.5% of which was attributable to use of brand medications. The mean costs of medications were $228 and $324 for those undergoing 1 and 2 surgeries, respectively. Topical antibiotics (89%) were the most commonly prescribed drug class by volume, followed by topical steroids (86%) and nonsteroidal anti-inflammatory drugs (66%), and accounted for 26%, 37%, and 36% of the total cataract surgery eye drop cost, respectively. Use of therapeutic and generic alternatives could have resulted in cost savings of as much as $118 million, or 70% of the total cost of postoperative eye drops. In adjusted analysis, patient factors associated with increased eye drop cost included older age, female gender, and race or ethnicity. Physician characteristics associated with increased eye drop cost included female gender, greater number of years in practice, practicing in metropolitan versus nonmetropolitan areas, and practicing in the Northeast versus the South and in the South versus the Midwest. CONCLUSIONS: The cost to the Centers for Medicare and Medicaid Services for eye drops prescribed for postoperative use after cataract surgery in 2016 was approximately $170 million. In the absence of evidence of clinical superiority of expensive versus less costly options, substantial opportunity exists to improve the value of care delivered to Medicare beneficiaries.