The global distribution of oral and maxillofacial surgeons: a mixed-methods study.

Despite its role in treating the most dominant non-communicable diseases worldwide, the global workforce of oral and maxillofacial (OM) surgeons is not well-characterized. To address the current deficit in understanding of the global OM surgeon workforce and to elevate oral and maxillofacial surgery (OMS) in the global health discourse, we join other surgical specialties in evaluating global surgical capacity with a descriptive analysis of the distribution of OM surgeons worldwide. A mixed-methods study was implemented using a combination of literature review, in-country contacts, internet searches, and survey data. The survey was distributed globally from January to June 2022. Data regarding OM surgeon workforce estimates were obtained for 104 of 195 United Nations-recognized countries (53.3%). Among countries with available estimates, the median global workforce density was 0.518 OM surgeons per 100,000 population. Twenty-eight countries (26.9%) were reported to have two or fewer OM surgeons. The median OM surgeon workforce density for low-income countries was 0.015 surgeons per 100,000 population, compared to 1.087 surgeons per 100,000 population in high-income countries. low and middle-income countries countries have the least workforce density as well as the least data coverage. More work is needed to better understand the capacity of the global OM surgeon workforce and access to OMS care.

Long term survival of Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis: letter to the Editor.

We read the article by Chuan YY et al (1) with interest when we searched the literature to guide our care for a patient with Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis. Chuan YY et al (1) reported a patient with EATL developed intracranial involvement and died nine months after the initial diagnosis. They also summarized previous studies and found the survival after initial diagnosis was no longer than sixteen months.

Quantification of bone marrow interstitial pH and calcium concentration by intravital ratiometric imaging.

The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca2+]e), but the local [Ca2+]e around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca2+]e in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca2+]e in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca2+]e (1.5 ± 0.57 mM). With aging, a significant increase in [Ca2+]e is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca2+]e and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.

The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

Establishment of feline in-house reference intervals for hematologic and biochemical parameters and potential age-related differences.

Reference intervals (RIs) are one of the essential elements in the procedure of disease diagnosis. This is especially true for feline species in which RI is less available than in canine species. RIs are affected by biological, geographical and instrumental factors, yet published RIs with incomplete background are popularly used. Inappropriate interpretations of RIs may affect classification of disease and subsequent treatment. In this study, we demonstrated the step-by-step establishment of feline RIs following the American Society for Veterinary Clinical Pathology (ASVCP) reference interval guideline. A total of 51 parameters were examined, including 20 hematology and 31 biochemistry parameters, and the results were compared to one local RI and two foreign RIs. Overall, about 29% (10/35) of tested parameters were different form local RIs and 60% (30/50) were different from the two foreign RIs, highlighting geographical variations. A higher upper reference limit (URL) in red blood cell count (RBC), hematocrit (Hct), Hemoglobin (Hgb), albumin, creatinine and lower URL in potassium and white blood cell count (WBC) were identified, which may impact the interpretation. In addition, statistical analysis of age and gender were factored separately and indicated that 10 parameters were significantly higher in the adult group. For the impact of gender, percentage of basophil and total iron-binding capacity (TIBC) were lower in female and male cats, respectively. In conclusion, we have demonstrated that it is desirable to establish in-house RIs or RIs of local sources. An age specific RI for the geriatric feline population is advisable for better diagnosis and monitoring the disease.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

High-quality thulium iron garnet films with tunable perpendicular magnetic anisotropy by off-axis sputtering - correlation between magnetic properties and film strain.

Thulium iron garnet (TmIG) films with perpendicular magnetic anisotropy (PMA) were grown on gadolinium gallium garnet (GGG) (111) substrates by off-axis sputtering. High-resolution synchrotron radiation X-ray diffraction studies and spherical aberration-corrected scanning transmission electron microscope (Cs-corrected STEM) images showed the excellent crystallinity of the films and their sharp interface with GGG. Damping constant of TmIG thin film was determined to be 0.0133 by frequency-dependent ferromagnetic resonance (FMR) measurements. The saturation magnetization (Ms) and the coercive field (Hc) were obtained systematically as a function of the longitudinal distance (L) between the sputtering target and the substrate. A 170% enhancement of PMA field (H⊥) was achieved by tuning the film composition to increase the tensile strain. Moreover, current-induced magnetization switching on a Pt/TmIG structure was demonstrated with an ultra-low critical current density (jc) of 2.5 × 106 A/cm2, an order of magnitude smaller than the previously reported value. We were able to tune Ms, Hc and H⊥ to obtain an ultra-low jc of switching the magnetization, showing the great potential of sputtered TmIG films for spintronics.

A novel ANO5 splicing variant in a LGMD2L patient leads to production of a truncated aggregation-prone Ano5 peptide.

Mutations in ANO5 cause several human diseases including gnathodiaphyseal dysplasia 1 (GDD1), limb-girdle muscular dystrophy 2L (LGMD2L), and Miyoshi myopathy 3 (MMD3). Previous work showed that complete genetic disruption of Ano5 in mice did not recapitulate human muscular dystrophy, while residual expression of mutant Ano5 in a gene trapped mouse developed muscular dystrophy with defective membrane repair. This suggests that truncated Ano5 expression may be pathogenic. Here, we screened a panel of commercial anti-Ano5 antibodies using a recombinant adenovirus expressing human Ano5 with FLAG and YFP at the N- and C-terminus, respectively. The monoclonal antibody (mAb) N421A/85 was found to specifically detect human Ano5 by immunoblotting and immunofluorescence staining. The antigen epitope was mapped to a region of 28 residues within the N-terminus. Immunofluorescence staining of muscle cryosections from healthy control subjects showed that Ano5 is localized at the sarcoplasmic reticulum. The muscle biopsy from a LGMD2L patient homozygous for the c.191dupA mutation showed no Ano5 signal, confirming the specificity of the N421A/85 antibody. Surprisingly, strong Ano5 signal was detected in a patient with compound heterozygous mutations (c.191dupA and a novel splice donor site variant c.363 + 4A > G at the exon 6-intron 6 junction). Interestingly, insertion of the mutant intron 6, but not the wild-type intron 6, into human ANO5 cDNA resulted in a major transcript that carried the first 158-bp of intron 6. Transfection of the construct encoding the first 121 amino acids into C2C12 cells resulted in protein aggregate formation, suggesting that aggregate-forming Ano5 peptide may contribute to the pathogenesis of muscular dystrophy.

Characterization and virus susceptibility of a continuous cell line derived from the brain of Aequidens rivulatus (Günther).

Cell cultures derived from the brain tissues of Aequidens rivulatus (Günther) have been characterized previously. In this study, a continuous cell line ARB8 was further established, and its growth characteristics, transcription and susceptibility to fish viruses-including chum salmon reovirus (CSV), marbled eel infectious pancreative necrosis virus (MEIPNV), grouper nervous necrosis virus (GNNV), giant seaperch iridovirus (GSIV), red seabream iridovirus (RSIV), koi herpesvirus (KHV), herpesvirus anguilla (HVA) and marbled eel polyoma-like virus (MEPyV)-were examined. ARB8 cells that showed epithelioid morphology and were passaged >80 times grew well at temperatures ranging from 25°C to 30°C in L-15 medium containing 5%-15% foetal bovine serum. The cells constitutively transcribed connexion 43, glutamine synthetase, nestin and nkx6-2, which are markers for neural progenitor cells. The cells were highly susceptible to CSV, MEIPNV, GSIV and RSIV and showed the typical cytopathic effect (CPE). However, the cells were resistant to GNNV, KHV, HVA and MEPyV because no significant CPE was noted after infection. Optimal temperatures for virus production ranged from 25°C to 30°C. The results revealed that the neural progenitor cell line ARB8 can potentially serve as a useful tool for investigating fish viruses and isolating new viruses in ornamental cichlid fishes.

Reproductive biology of female striped marlin Kajikia audax in the western Pacific Ocean.

Length and mass data for 1260 (536 females, 683 males, 41 sex unknown) striped marlin Kajikia audax were collected at the fish markets of Tungkang, Singkang and Nanfangao from July 2004 to September 2010. Of these samples, 534 gonads (236 females and 298 males) ranging from 95 to 206 cm in eye-to-fork length (LEF ) and 8 to 88 kg in round mass (MR ), were collected. Chi-square tests indicated sex ratios were homogeneous among months in 2004 and 2006-2008, but not in 2005, 2009 and 2010; and there were significant differences in sex ratio by size. The overall sex ratio (RS ) differed significantly from the expected 0·5. Kajikia audax are sexually dimorphic and the proportions of females increased with size between 140 and 210 cm LEF . Reproductive activity was assessed using a gonado-somatic index (IG ), external appearance of the gonads and histological examination and results indicated that the spawning season occurred from April to August with a peak in June to July. Based on histological observations and the distribution of oocyte diameters, K. audax are multiple spawners and their oocytes develop asynchronously. The estimated length-at-50% maturity (LEF50 ) was c. 181 cm (c. 4·8 years of age) for females. The proportion of reproductively active females in the spawning season with ovaries containing postovulatory follicles (0·27) indicated that they spawned every 3·7 days on average. The hydrated oocyte method estimated mean ± S.D. batch fecundity (FB ) to be 4·4 ± 2·02 million eggs; average relative fecundity was 53·6 ± 13·9 oocytes g-1 MR ; and the average annual fecundity was 181·3 ± 48·3 million eggs. The parameters estimated in this study are key information for stock assessments of K. audax in the north-western and central Pacific and will contribute to the conservation, management and sustainable yield of this species.

Androgen receptor promotes melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signals.

Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared with AR-negative melanoma patients. Here we report that AR can have positive roles to increase melanoma cell invasion in multiple cell lines in vitro and a mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13 signaling to increase MITF protein degradation through a reduction of de-ubiquitination. Restoring MITF can reverse AR-enhanced melanoma cell invasion. Together, our results demonstrate that AR can promote melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly identified signal with AR degradation enhancer ASC-J9 may help us to better suppress the melanoma metastasis.

Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

OBJECTIVES: To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mia ' records. BACKGROUND: The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mia ') are identified in 1·24% of our population, and anti-'Mia ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mia ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mia '-related transfusion reactions. METHODS: Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mia '-positive serum were selected for blood recipients with anti-'Mia ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. RESULTS: The transfusion reaction rate was significantly higher in anti-'Mia '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mia ' became similar to total blood recipients. IgG form anti-'Mia ' antibodies were present in all cases of probable anti-'Mia '-related transfusion reactions. The time required for anti-'Mia ' boosting after transfusion was around 4-21 days. CONCLUSION: Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mia ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mia ' is prevalent.

Development of a millimetrically scaled biodiesel transesterification device that relies on droplet-based co-axial fluidics.

In this study, we investigated a fluidic system that adheres to new concepts of energy production. To improve efficiency, cost, and ease of manufacture, a millimetrically scaled device that employs a droplet-based co-axial fluidic system was devised to complete alkali-catalyzed transesterification for biodiesel production. The large surface-to-volume ratio of the droplet-based system, and the internal circulation induced inside the moving droplets, significantly enhanced the reaction rate of immiscible liquids used here - soybean oil and methanol. This device also decreased the molar ratio between methanol and oil to near the stoichiometric coefficients of a balanced chemical equation, which enhanced the total biodiesel volume produced, and decreased the costs of purification and recovery of excess methanol. In this work, the droplet-based co-axial fluidic system performed better than other methods of continuous-flow production. We achieved an efficiency that is much greater than that of reported systems. This study demonstrated the high potential of droplet-based fluidic chips for energy production. The small energy consumption and low cost of the highly purified biodiesel transesterification system described conforms to the requirements of distributed energy (inexpensive production on a moderate scale) in the world.

Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemoresistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals.

Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) and are associated with PCa progression. As the current androgen deprivation therapy with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here, we found NEPCa cells could increase the docetaxel resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed that NEPCa could increase the docetaxel resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or shPTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa.

Short-term dipeptidyl peptidase-4 inhibitor use increases the risk of herpes zoster infection in Asian patients with diabetes.

BACKGROUND: We aimed to evaluate whether patients with diabetes who use dipeptidyl peptidase (DPP)-4 inhibitors are at a higher risk of developing a herpes zoster (HZ) infection. METHODS: We used a subset of the Longitudinal Health Insurance Database 2000 containing all inpatient and outpatient medical claims of ∼1 million people who were randomly sampled from the National Health Insurance Research Database. Patients who were newly diagnosed with Type 2 diabetes International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM 250.x0 and 250.x2) who used antidiabetic medications were divided into two cohorts based on their use of DPP-4 inhibitors between 2009 and 2011. Cox proportion hazard regression models were used to assess the effects of DPP-4 inhibitors on the incidence of HZ compared with the non-DPP-4-inhibitor-exposed cohort. RESULTS: Patients in DPP-4-inhibitor-exposed cohort with diabetes and HZ infections revealed an incidence density of 4.20 per 1000 person-years compared with 3.50 per 1000 person-years for the non-DPP-4-inhibitor-exposed cohort (adjusted hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 0.70-1.99). Furthermore, high-dose DPP-4-inhibitor treatment was associated with a significantly higher risk of HZ (adjusted HR = 2.46, 95% CI = 1.16-5.19 for a defined daily dose [DDD] ≥ 360). In addition, short-term DPP-4-inhibitor treatment was associated with a significantly higher risk of HZ (adjusted HR = 2.04, 95% CI = 1.03-4.04 for a DDD ≥ 360 days). CONCLUSION: These results suggest that Asian patients with diabetes who use short-term DPP-4 inhibitors might be at a higher risk of developing HZ.

Adaptive Phase-Field Modeling of Anisotropic Wetting with Line Tension at the Triple Junction.

Line tension could affect the contact angle at triple junction, especially in micro- to nanoscale wetting. We have developed an adaptive phase-field model to consider the line tension quantitatively. This model is coupled to the smoothed boundary method for treating the contact line with the solid phase, while the volume constraint is imposed. Our calculated contact angles are in good agreement with the modified Young's equation. Further examples are illustrated for the anisotropic wetting on hydrophilic/hydrophobic stripes and rectangular grooves.

Statins can increase the risk of herpes zoster infection in Asia.

This study evaluated whether statin therapy increases the risk of herpes zoster (HZ) infection in Asia. This retrospective cohort study used the Longitudinal Health Insurance Database (LHID2000). From the LHID2000, patients aged 20 years were divided into two cohorts according to their statin use and were matched at a 1:1 ratio according to propensity scores, which were calculated using a logistic regression for estimating the probability of treatment assignment. The primary outcome was HZ infection. All patients were followed from the index date until the date of HZ infection, withdrawal from the insurance system, or the end of 2011. The study included 53,069 patients receiving statin therapy as a statin cohort and 53,069 patients without statin therapy as a nonstatin cohort. The mean follow-up durations for the statin cohort and nonstatin cohort were 4.89 [standard deviation (SD) = 2.86] years and 4.75 (SD = 2.90) years, respectively. The patients in the statin cohort had a 21 % higher risk of contracting HZ infection than the patients in the nonstatin cohort [95 % confidence interval (CI) = 1.13-1.29]. The incidence of HZ infection increased with the Charlson comorbidity index (CCI) score in both cohorts. A high mean defined daily dose of the six types of statins considered in this study was associated with a significantly increased risk of HZ infection. Statin therapy can increase HZ infection in Asia. More benefit-risk evaluations for statin use are necessary in Asia.